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Developmentally inspired synthetic kidney engineering

Nature Biotechnology (2026)Cite this article

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Abstract

Developmentally inspired kidney tissues derived from stem cells hold promise for future renal replacement tissue, but clinical translation is limited by variability in outcomes, absence of cell types, lack of functional maturity and implausible scalability. Overcoming these may benefit from tissue engineering strategies that leverage processes for tissue construction that the embryonic kidney uses to achieve its diverse and parallelized functions. We present a ‘developmental engineering’ strategy in which spatial and temporal cues inspired by in vivo development guide multiscale structure formation in vitro. We highlight emerging tools in synthetic biology, spatial patterning and control over tissue microenvironments that can set initial and boundary conditions to instigate and guide the development of a desired ‘motif’. We then present a vision for scalable developmental engineering by guiding and daisy-chaining tissue motifs, bridging discontinuities in self-organization via direct assembly. Although we articulate a blueprint for developmental engineering of translationally viable renal replacement tissues, the strategy is also applicable to other solid organs.

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Fig. 1: Metanephric kidney development parallelizes nephron-forming stem cell niches.
Fig. 2: Developmental engineering strategy: setting initial and boundary conditions that guide self-organization within a target motif.
Fig. 3: Controlling developmental motifs through initial and boundary conditions.
Fig. 4: Developmental engineering of the NP and UB lineages.
Fig. 5: Developmental engineering of the stroma and vasculature.

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References

  1. McMahon, A. P. Development of the mammalian kidney. Curr. Top. Dev. Biol. 117, 31–64 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tekguc, M. et al. Kidney organoids: a pioneering model for kidney diseases. Transl. Res. 250, 1–17 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. US Department of Health and Human Services. Advancing American kidney health https://aspe.hhs.gov/system/files/pdf/262046/AdvancingAmericanKidneyHealth.pdf (2019).

  4. Kidney Health Initiative. Technology roadmap for innovative approaches to renal replacement therapy https://www.asn-online.org/g/blast/files/KHI_RRT_Roadmap1.0_FINAL_102318_web.pdf (2018).

  5. US Food and Drug Administration. FDA announces plan to phase out animal testing requirement for monoclonal antibodies and other drugs https://www.fda.gov/news-events/press-announcements/fda-announces-plan-phase-out-animal-testing-requirement-monoclonal-antibodies-and-other-drugs (2025).

  6. National Institutes of Health. NIH to prioritize human-based research technologies https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies (2025).

  7. Dorison, A., Forbes, T. A. & Little, M. H. What can we learn from kidney organoids?. Kidney Int. 102, 1013–1029 (2022).

    Article  PubMed  Google Scholar 

  8. Little, M. H. & McMahon, A. P. Mammalian kidney development: principles, progress, and projections. Cold Spring Harb. Perspect. Biol. 4, a008300 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Morizane, R. et al. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat. Biotechnol. 33, 1193–1200 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Takasato, M. et al. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat. Cell Biol. 16, 118–126 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Vanslambrouck, J. M., Tan, K. S., Mah, S. & Little, M. H. Generation of proximal tubule-enhanced kidney organoids from human pluripotent stem cells. Nat. Protoc. 18, 3229–3252 (2023).

    Article  CAS  PubMed  Google Scholar 

  12. Li, Z. & Lindström, N. O. Building a kidney tree: functional collecting duct from human pluripotent stem cells. Dev. Cell 57, 2251–2253 (2022).

    Article  CAS  PubMed  Google Scholar 

  13. Shi, M., Fu, P., Bonventre, J. V. & McCracken, K. W. Directed differentiation of ureteric bud and collecting duct organoids from human pluripotent stem cells. Nat. Protoc. 18, 2485–2508 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Little, M. H. & Combes, A. N. Kidney organoids: accurate models or fortunate accidents. Genes Dev. 33, 1319–1345 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Adler, M. et al. Emergence of division of labor in tissues through cell interactions and spatial cues. Cell Rep. 42, 112412 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Steinberg, M. S. Reconstruction of tissues by dissociated cells. Science 141, 401–408 (1963).

    Article  CAS  PubMed  Google Scholar 

  17. Brassard, J. A. & Lutolf, M. P. Engineering stem cell self-organization to build better organoids. Cell Stem Cell 24, 860–876 (2019).

    Article  CAS  PubMed  Google Scholar 

  18. Pfeifer, C. R., Shyer, A. E. & Rodrigues, A. R. Creative processes during vertebrate organ morphogenesis: biophysical self-organization at the supracellular scale. Curr. Opin. Cell Biol. 86, 102305 (2024).

    Article  CAS  PubMed  Google Scholar 

  19. Li, R. & Bowerman, B. Symmetry breaking in biology. Cold Spring Harb. Perspect. Biol. 2, a003475 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lancaster, M. A. & Knoblich, J. A. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345, 1247125 (2014).

    Article  PubMed  Google Scholar 

  21. Serra, D. et al. Self-organization and symmetry breaking in intestinal organoid development. Nature 569, 66–72 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Srivastava, V. et al. Configurational entropy is an intrinsic driver of tissue structural heterogeneity. Preprint at bioRxiv https://doi.org/10.1101/2023.07.01.546933 (2023).

  23. Cerchiari, A. E. et al. A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity. Proc. Natl Acad. Sci. USA 112, 2287–2292 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Garner, R. M., McGeary, S. E., Klein, A. M. & Megason, S. G. Tissue fluidity mediates a trade-off between the speed and accuracy of multicellular patterning by cell sorting. Biophys. J. 124, 4157–4175 (2025).

    Article  CAS  PubMed  Google Scholar 

  25. Garreta, E. et al. Rethinking organoid technology through bioengineering. Nat. Mater. 20, 145–155 (2021).

    Article  CAS  PubMed  Google Scholar 

  26. Sasai, Y. Cytosystems dynamics in self-organization of tissue architecture. Nature 493, 318–326 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. Lefevre, J. G. et al. Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells. Development 144, 1087–1096 (2017).

    CAS  PubMed  Google Scholar 

  28. Leclerc, K. & Costantini, F. Mosaic analysis of cell rearrangements during ureteric bud branching in dissociated/reaggregated kidney cultures and in vivo. Dev. Dyn. 245, 483–496 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Taguchi, A. & Nishinakamura, R. Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell 21, 730–746 (2017).

    Article  CAS  PubMed  Google Scholar 

  30. Brassard, J. A., Nikolaev, M., Hübscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22–29 (2021).

    Article  CAS  PubMed  Google Scholar 

  31. Laurent, J. et al. Convergence of microengineering and cellular self-organization towards functional tissue manufacturing. Nat. Biomed. Eng. 1, 939–956 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Autorino, C. & Petridou, N. I. Critical phenomena in embryonic organization. Curr. Opin. Syst. Biol. 31, 100433 (2022).

    Article  CAS  Google Scholar 

  33. Force, E., Lamy, D., Debernard, S., Savouré, A. & Dacher, M. Developmental transitions involve common biological processes across living beings. Heliyon 11, e42995 (2025).

    Article  CAS  Google Scholar 

  34. Levin, M. et al. The mid-developmental transition and the evolution of animal body plans. Nature 531, 637–641 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rankin, S. A. et al. Timing is everything: reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis. Dev. Biol. 434, 121–132 (2018).

    Article  CAS  PubMed  Google Scholar 

  36. Waddington, C. H. The Strategy of the Genes (Routledge, 2015).

  37. Barresi, M. J. F. & Gilbert, S. F. Developmental Biology (Oxford University Press, 2020).

  38. Metzger, R. J., Klein, O. D., Martin, G. R. & Krasnow, M. A. The branching programme of mouse lung development. Nature 453, 745–750 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sznurkowska, M. K. et al. Defining lineage potential and fate behavior of precursors during pancreas development. Dev. Cell 46, 360–375 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jheon, A. H., Seidel, K., Biehs, B. & Klein, O. D. From molecules to mastication: the development and evolution of teeth. Wiley Interdiscip. Rev. Dev. Biol. 2, 165–182 (2013).

    Article  PubMed  Google Scholar 

  41. Buijtendijk, M. F. J., Barnett, P. & van den Hoff, M. J. B. Development of the human heart. Am. J. Med. Genet. C Semin. Med. Genet. 184, 7–22 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Fuhrmann, S. Eye morphogenesis and patterning of the optic vesicle. Curr. Top. Dev. Biol. 93, 61–84 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gjorevski, N. et al. Tissue geometry drives deterministic organoid patterning. Science 375, eaaw9021 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Short, K. M. et al. Global quantification of tissue dynamics in the developing mouse kidney. Dev. Cell 29, 188–202 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. Mugford, J. W., Yu, J., Kobayashi, A. & McMahon, A. P. High-resolution gene expression analysis of the developing mouse kidney defines novel cellular compartments within the nephron progenitor population. Dev. Biol. 333, 312–323 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Brown, A. C. et al. Role for compartmentalization in nephron progenitor differentiation. Proc. Natl Acad. Sci. USA 110, 4640–4645 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Prahl, L. S. et al. Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses. Nat. Mater. 23, 1582–1591 (2024).

  48. Prahl, L. S., Viola, J. M., Liu, J. & Hughes, A. J. The developing murine kidney actively negotiates geometric packing conflicts to avoid defects. Dev. Cell 58, 110–120 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lefevre, J. G. et al. Branching morphogenesis in the developing kidney is governed by rules that pattern the ureteric tree. Development 144, 4377–4385 (2017).

    CAS  PubMed  Google Scholar 

  50. Grindel, S. H. et al. A mechanical pacemaker sets rhythmic nephron formation in the kidney. Preprint at bioRxiv https://doi.org/10.1101/2023.11.21.568157 (2025).

  51. Porter, C. M., Qian, G. C., Grindel, S. H. & Hughes, A. J. Highly parallel production of designer organoids by mosaic patterning of progenitors. Cell Syst. 15, 649–661 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Selden, N. S. et al. Chemically programmed cell adhesion with membrane-anchored oligonucleotides. J. Am. Chem. Soc. 134, 765–768 (2012).

    Article  CAS  PubMed  Google Scholar 

  53. Todhunter, M. E. et al. Programmed synthesis of three-dimensional tissues. Nat. Methods 12, 975–981 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Viola, J. M. et al. Guiding cell network assembly using shape-morphing hydrogels. Adv. Mater. 32, e2002195 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Weber, R. J., Liang, S. I., Selden, N. S., Desai, T. A. & Gartner, Z. J. Efficient targeting of fatty-acid modified oligonucleotides to live cell membranes through step-wise assembly. Biomacromolecules 15, 4621–4626 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zandrini, T., Florczak, S., Levato, R. & Ovsianikov, A. Breaking the resolution limits of 3D bioprinting: future opportunities and present challenges. Trends Biotechnol. 41, 604–614 (2023).

    Article  CAS  PubMed  Google Scholar 

  57. Lawlor, K. T. et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat. Mater. 20, 260–271 (2021).

    Article  CAS  PubMed  Google Scholar 

  58. Skylar-Scott, M. A. et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 5, eaaw2459 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Singh, N. K. et al. Three-dimensional cell-printing of advanced renal tubular tissue analogue. Biomaterials 232, 119734 (2020).

    Article  CAS  PubMed  Google Scholar 

  60. Lin, N. Y. C. et al. Renal reabsorption in 3D vascularized proximal tubule models. Proc. Natl Acad. Sci. USA 116, 5399–5404 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wolf, K. J., Weiss, J. D., Uzel, S. G. M., Skylar-Scott, M. A. & Lewis, J. A. Biomanufacturing human tissues via organ building blocks. Cell Stem Cell 29, 667–677 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Osathanondh, V. & Potter, E. L. Development of human kidney as shown by microdissection. III. Formation and interrelationship of collecting tubules and nephrons. Arch. Pathol. 76, 290–302 (1963).

    CAS  PubMed  Google Scholar 

  63. Hughes, A. J. et al. Engineered tissue folding by mechanical compaction of the mesenchyme. Dev. Cell 44, 165–178 (2018).

    Article  CAS  PubMed  Google Scholar 

  64. Taguchi, A. et al. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell 14, 53–67 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Freedman, B. S. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat. Commun. 6, 8715 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Howden, S. E. & Little, M. H. Generating kidney organoids from human pluripotent stem cells using defined conditions. Methods Mol. Biol. 2155, 183–192 (2020).

    Article  CAS  PubMed  Google Scholar 

  67. Morizane, R. & Bonventre, J. V. Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells. Nat. Protoc. 12, 195–207 (2017).

    Article  CAS  PubMed  Google Scholar 

  68. Mae, S.-I. et al. Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential. Cell Rep. 32, 107963 (2020).

    Article  CAS  PubMed  Google Scholar 

  69. Takasato, M., Er, P. X., Chiu, H. S. & Little, M. H. Generation of kidney organoids from human pluripotent stem cells. Nat. Protoc. 11, 1681–1692 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zeng, Z. et al. Generation of patterned kidney organoids that recapitulate the adult kidney collecting duct system from expandable ureteric bud progenitors. Nat. Commun. 12, 3641 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Howden, S. E., Vanslambrouck, J. M., Wilson, S. B., Tan, K. S. & Little, M. H. Reporter-based fate mapping in human kidney organoids confirms nephron lineage relationships and reveals synchronous nephron formation. EMBO Rep. 20, e47483 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Vanslambrouck, J. M. et al. A toolbox to characterize human induced pluripotent stem cell-derived kidney cell types and organoids. J. Am. Soc. Nephrol. 30, 1811–1823 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. McNamara, H. M., Solley, S. C., Adamson, B., Chan, M. M. & Toettcher, J. E. Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking. Nat. Cell Biol. 26, 1832–1844 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cebrian, C., Asai, N., D’Agati, V. & Costantini, F. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment. Cell Rep. 7, 127–137 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Velazquez, J. J. et al. Gene regulatory network analysis and engineering directs development and vascularization of multilineage human liver organoids. Cell Syst. 12, 41–55 (2021).

    Article  CAS  PubMed  Google Scholar 

  76. Skylar-Scott, M. A. et al. Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues. Nat. Biomed. Eng. 6, 449–462 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Legnini, I. et al. Spatiotemporal, optogenetic control of gene expression in organoids. Nat. Methods 20, 1544–1552 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Suh, K. et al. Large-scale control over collective cell migration using light-activated epidermal growth factor receptors. Cell Syst. 16, 101203 (2025).

    Article  CAS  PubMed  Google Scholar 

  79. Karner, C. M. et al. Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development. Development 138, 1247–1257 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lawlor, K. T. et al. Nephron progenitor commitment is a stochastic process influenced by cell migration. eLife 8, e41156 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Mederacke, M., Conrad, L., Doumpas, N., Vetter, R. & Iber, D. Geometric effects position renal vesicles during kidney development. Cell Rep. 42, 113526 (2023).

    Article  CAS  PubMed  Google Scholar 

  82. Ramalingam, H. et al. Disparate levels of β-catenin activity determine nephron progenitor cell fate. Dev. Biol. 440, 13–21 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. O’Brien, L. L. et al. Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment. eLife 7, e40392 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Anand, G. M. et al. Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation. Cell 186, 497–512 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. van Oostrom, M. J. et al. Coupling of cell proliferation to the segmentation clock ensures robust somite scaling. Preprint at bioRxiv https://doi.org/10.1101/2025.01.10.632257 (2025).

  86. Hubaud, A. & Pourquié, O. Signalling dynamics in vertebrate segmentation. Nat. Rev. Mol. Cell Biol. 15, 709–721 (2014).

    Article  CAS  PubMed  Google Scholar 

  87. Peng, Z. et al. Somites are a source of nephron progenitors in zebrafish. Nat. Commun. 16, 6914 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hayashi, S., Suzuki, H. & Takemoto, T. The nephric mesenchyme lineage of intermediate mesoderm is derived from TBX6-expressing derivatives of neuro-mesodermal progenitors via BMP-dependent OSR1 function. Dev. Biol. 478, 155–162 (2021).

    Article  CAS  PubMed  Google Scholar 

  89. Soueid-Baumgarten, S., Yelin, R., Davila, E. K. & Schultheiss, T. M. Parallel waves of inductive signaling and mesenchyme maturation regulate differentiation of the chick mesonephros. Dev. Biol. 385, 122–135 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Sanaki-Matsumiya, M. et al. Periodic formation of epithelial somites from human pluripotent stem cells. Nat. Commun. 13, 2325 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Miao, Y. et al. Reconstruction and deconstruction of human somitogenesis in vitro. Nature 614, 500–508 (2023).

    Article  CAS  PubMed  Google Scholar 

  92. Engleka, K. A. et al. Insertion of Cre into the Pax3 locus creates a new allele of Splotch and identifies unexpected Pax3 derivatives. Dev. Biol. 280, 396–406 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Canty, L., Zarour, E., Kashkooli, L., François, P. & Fagotto, F. Sorting at embryonic boundaries requires high heterotypic interfacial tension. Nat. Commun. 8, 157 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Manning, M. L., Foty, R. A., Steinberg, M. S. & Schoetz, E.-M. Coaction of intercellular adhesion and cortical tension specifies tissue surface tension. Proc. Natl Acad. Sci. USA 107, 12517–12522 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Combes, A. N., Davies, J. A. & Little, M. H. Cell–cell interactions driving kidney morphogenesis. Curr. Top. Dev. Biol. 112, 467–508 (2015).

    Article  CAS  PubMed  Google Scholar 

  96. Liu, J., Prahl, L. S., Huang, A. Z. & Hughes, A. J. Measurement of adhesion and traction of cells at high yield reveals an energetic ratchet operating during nephron condensation. Proc. Natl Acad. Sci. USA 121, e2404586121 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Morsut, L. et al. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 164, 780–791 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Toda, S., Blauch, L. R., Tang, S. K. Y., Morsut, L. & Lim, W. A. Programming self-organizing multicellular structures with synthetic cell–cell signaling. Science 361, 156–162 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Stevens, A. J. et al. Programming multicellular assembly with synthetic cell adhesion molecules. Nature 614, 144–152 (2023).

    Article  CAS  PubMed  Google Scholar 

  100. Georgas, K. et al. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev. Biol. 332, 273–286 (2009).

    Article  CAS  PubMed  Google Scholar 

  101. Fausto, C. C. et al. Defining and controlling axial nephron patterning in human kidney organoids with synthetic Wnt-secreting organizers. Preprint at bioRxiv https://doi.org/10.1101/2024.11.30.626171 (2024).

  102. Lindström, N. O. et al. Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron. eLife 3, e04000 (2015).

    Article  PubMed  Google Scholar 

  103. Takasato, M. et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 564–568 (2015).

    Article  CAS  PubMed  Google Scholar 

  104. Vanslambrouck, J. M. et al. Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids. Nat. Commun. 13, 5943 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yamada, T. et al. Synthetic organizer cells guide development via spatial and biochemical instructions. Cell 188, 778–795 (2025).

    Article  CAS  PubMed  Google Scholar 

  106. Martyn, I., Kanno, T. Y., Ruzo, A., Siggia, E. D. & Brivanlou, A. H. Self-organization of a human organizer by combined Wnt and Nodal signalling. Nature 558, 132–135 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Shi, M. et al. Integrating collecting systems in human kidney organoids through fusion of distal nephron to ureteric bud. Cell Stem Cell 32, 1055–1070 (2025).

    Article  CAS  PubMed  Google Scholar 

  108. Ballermann, B. J. Glomerular endothelial cell differentiation. Kidney Int. 67, 1668–1671 (2005).

    Article  PubMed  Google Scholar 

  109. Chang, C.-H. & Davies, J. A. In developing mouse kidneys, orientation of loop of Henle growth is adaptive and guided by long-range cues from medullary collecting ducts. J. Anat. 235, 262–270 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lancaster, M. A. et al. Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 35, 659–666 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nerger, B. A. et al. 3D hydrogel encapsulation regulates nephrogenesis in kidney organoids. Adv. Mater. 36, e2308325 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Lang, C., Conrad, L. & Iber, D. Organ-specific branching morphogenesis. Front. Cell Dev. Biol. 9, 671402 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Chi, X. et al. RET-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis. Dev. Cell 17, 199–209 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Packard, A., Klein, W. H. & Costantini, F. RET signaling in ureteric bud epithelial cells controls cell movements, cell clustering and bud formation. Development 148, dev199386 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Riccio, P., Cebrian, C., Zong, H., Hippenmeyer, S. & Costantini, F. RET and ETV4 promote directed movements of progenitor cells during renal branching morphogenesis. PLoS Biol. 14, e1002382 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Shakya, R., Watanabe, T. & Costantini, F. The role of GDNF/RET signaling in ureteric bud cell fate and branching morphogenesis. Dev. Cell 8, 65–74 (2005).

    Article  CAS  PubMed  Google Scholar 

  117. Costantini, F. Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation 74, 402–421 (2006).

    Article  CAS  PubMed  Google Scholar 

  118. Qiao, J., Sakurai, H. & Nigam, S. K. Branching morphogenesis independent of mesenchymal–epithelial contact in the developing kidney. Proc. Natl Acad. Sci. USA 96, 7330–7335 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Shi, M. et al. Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. Nat. Biotechnol. 41, 252–261 (2023).

    Article  CAS  PubMed  Google Scholar 

  120. Howden, S. E. et al. Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk. Cell Stem Cell 28, 671–684 (2021).

    Article  CAS  PubMed  Google Scholar 

  121. Shakya, R. et al. The role of GDNF in patterning the excretory system. Dev. Biol. 283, 70–84 (2005).

    Article  CAS  PubMed  Google Scholar 

  122. Basson, M. A. et al. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev. Cell 8, 229–239 (2005).

    Article  CAS  PubMed  Google Scholar 

  123. Basson, M. A. et al. Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev. Biol. 299, 466–477 (2006).

    Article  CAS  PubMed  Google Scholar 

  124. Goodwin, K. et al. Smooth muscle differentiation shapes domain branches during mouse lung development. Development 146, dev181172 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kim, H. Y. et al. Localized smooth muscle differentiation is essential for epithelial bifurcation during branching morphogenesis of the mammalian lung. Dev. Cell 34, 719–726 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Buchmann, B. et al. Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids. Nat. Commun. 12, 2759 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Wang, S., Matsumoto, K., Lish, S. R., Cartagena-Rivera, A. X. & Yamada, K. M. Budding epithelial morphogenesis driven by cell–matrix versus cell–cell adhesion. Cell 184, 3702–3716 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Harunaga, J. S., Doyle, A. D. & Yamada, K. M. Local and global dynamics of the basement membrane during branching morphogenesis require protease activity and actomyosin contractility. Dev. Biol. 394, 197–205 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Huang, A. Z. et al. Engineering kidney developmental trajectory using culture boundary conditions. Nat. Commun. 16, 7829 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Kurtzeborn, K. et al. Epithelial cell shape changes contribute to regulation of ureteric bud branching morphogenesis. FEBS J. 292, 6253–6282 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Carroll, T. J. & Yu, J. The kidney and planar cell polarity. Curr. Top. Dev. Biol. 101, 185–212 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Chakraborty, S., Peak, K. E., Gleghorn, J. P., Carroll, T. J. & Varner, V. D. Quantifying spatial patterns of tissue stiffness within the embryonic mouse kidney. Methods Mol. Biol. 2805, 171–186 (2024).

    Article  PubMed  Google Scholar 

  133. Tang, Z. et al. Mechanical forces program the orientation of cell division during airway tube morphogenesis. Dev. Cell 44, 313–325 (2018).

    Article  CAS  PubMed  Google Scholar 

  134. Packard, A. et al. Luminal mitosis drives epithelial cell dispersal within the branching ureteric bud. Dev. Cell 27, 319–330 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Menshykau, D. et al. Image-based modeling of kidney branching morphogenesis reveals GDNF–RET based Turing-type mechanism and pattern-modulating Wnt11 feedback. Nat. Commun. 10, 239 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Gsell, S., Tlili, S., Merkel, M. & Lenne, P.-F. Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids. Nat. Phys. 21, 644–653 (2025).

    Article  CAS  Google Scholar 

  137. Combes, A. N., Zappia, L., Er, P. X., Oshlack, A. & Little, M. H. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. Genome Med. 11, 3 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Uchimura, K., Wu, H., Yoshimura, Y. & Humphreys, B. D. Human pluripotent stem cell-derived kidney organoids with improved collecting duct maturation and injury modeling. Cell Rep. 33, 108514 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Montesano, R., Schaller, G. & Orci, L. Induction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors. Cell 66, 697–711 (1991).

    Article  CAS  PubMed  Google Scholar 

  140. Santos, O. F. & Nigam, S. K. HGF-induced tubulogenesis and branching of epithelial cells is modulated by extracellular matrix and TGF-β. Dev. Biol. 160, 293–302 (1993).

    Article  CAS  PubMed  Google Scholar 

  141. Ruiter, F. A. A. et al. Soft, dynamic hydrogel confinement improves kidney organoid lumen morphology and reduces epithelial–mesenchymal transition in culture. Adv. Sci. 9, e2200543 (2022).

    Article  Google Scholar 

  142. Peak, K. E. et al. Photo-induced changes in tissue stiffness alter epithelial budding morphogenesis in the embryonic lung. Preprint at bioRxiv https://doi.org/10.1101/2024.08.22.609268 (2024).

  143. Yavitt, F. M. et al. In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis. Sci. Adv. 9, eadd5668 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Morley, C. D. et al. Quantitative characterization of 3D bioprinted structural elements under cell generated forces. Nat. Commun. 10, 3029 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Gjorevski, N. & Nelson, C. M. Endogenous patterns of mechanical stress are required for branching morphogenesis. Integr. Biol. 2, 424–434 (2010).

    Article  CAS  Google Scholar 

  146. Tang, M. J., Worley, D., Sanicola, M. & Dressler, G. R. The RET–glial cell-derived neurotrophic factor (GDNF) pathway stimulates migration and chemoattraction of epithelial cells. J. Cell Biol. 142, 1337–1345 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Hyeon, B., Lee, H., Kim, N. & Heo, W. D. Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons. Mol. Brain 16, 56 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bugaj, L. J., Choksi, A. T., Mesuda, C. K., Kane, R. S. & Schaffer, D. V. Optogenetic protein clustering and signaling activation in mammalian cells. Nat. Methods 10, 249–252 (2013).

    Article  CAS  PubMed  Google Scholar 

  149. Town, J. P. & Weiner, O. D. Local negative feedback of Rac activity at the leading edge underlies a pilot pseudopod-like program for amoeboid cell guidance. PLoS Biol. 21, e3002307 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Hirashima, T. & Matsuda, M. ERK-mediated curvature feedback regulates branching morphogenesis in lung epithelial tissue. Curr. Biol. 34, 683–696 (2024).

    Article  CAS  PubMed  Google Scholar 

  151. Michos, O. et al. Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet. 6, e1000809 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Chau, A. H., Walter, J. M., Gerardin, J., Tang, C. & Lim, W. A. Designing synthetic regulatory networks capable of self-organizing cell polarization. Cell 151, 320–332 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Cavanaugh, K. E., Staddon, M. F., Munro, E., Banerjee, S. & Gardel, M. L. RhoA mediates epithelial cell shape changes via mechanosensitive endocytosis. Dev. Cell 52, 152–166 (2020).

    Article  CAS  PubMed  Google Scholar 

  154. Kao, R. M., Vasilyev, A., Miyawaki, A., Drummond, I. A. & McMahon, A. P. Invasion of distal nephron precursors associates with tubular interconnection during nephrogenesis. J. Am. Soc. Nephrol. 23, 1682–1690 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Tsujimoto, H. et al. A modular differentiation system maps multiple human kidney lineages from pluripotent stem cells. Cell Rep. 31, 107476 (2020).

    Article  CAS  PubMed  Google Scholar 

  156. Palakkan, A. A. et al. Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells. Sci. Rep. 12, 12573 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Wilson, S. B., Santos, I. P., Wildfang, L., Imsa, K. & Little, M. H. Generation of multi-lineage kidney assembloids with integration between nephrons and a single exiting collecting duct. Preprint at bioRxiv https://doi.org/10.1101/2025.02.27.640561 (2025).

  158. Huycke, T. R. et al. Patterning and folding of intestinal villi by active mesenchymal dewetting. Cell 187, 3072–3089 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. López-García, I. et al. Epithelial tubule interconnection driven by HGF–MET signaling in the kidney. Proc. Natl Acad. Sci. USA 121, e2416887121 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Kamei, C. N., Gallegos, T. F., Liu, Y., Hukriede, N. & Drummond, I. A. Wnt signaling mediates new nephron formation during zebrafish kidney regeneration. Development 146, dev168294 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. England, A. R. et al. Identification and characterization of cellular heterogeneity within the developing renal interstitium. Development 147, dev190108 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Wilson, S. B. & Little, M. H. The origin and role of the renal stroma. Development 148, dev199886 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Drake, K. A. et al. Transcription factors YAP/TAZ and SRF cooperate to specify renal myofibroblasts in the developing mouse kidney. J. Am. Soc. Nephrol. 33, 1694–1707 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Barry, D. M. et al. Molecular determinants of nephron vascular specialization in the kidney. Nat. Commun. 10, 5705 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Kobayashi, A. et al. Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Reports 3, 650–662 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Das, A. et al. Stromal–epithelial crosstalk regulates kidney progenitor cell differentiation. Nat. Cell Biol. 15, 1035–1044 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Rosselot, C. et al. Non-cell-autonomous retinoid signaling is crucial for renal development. Development 137, 283–292 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Hum, S., Rymer, C., Schaefer, C., Bushnell, D. & Sims-Lucas, S. Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning. PLoS ONE 9, e88400 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Levinson, R. S. et al. FOXD1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132, 529–539 (2005).

    Article  CAS  PubMed  Google Scholar 

  170. Rowan, C. J. et al. Hedgehog-GLI signaling in FOXD1-positive stromal cells promotes murine nephrogenesis via TGFβ signaling. Development 145, dev159947 (2018).

    Article  PubMed  Google Scholar 

  171. Fetting, J. L. et al. FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney. Development 141, 17–27 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Tanigawa, S. et al. Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma. Nat. Commun. 13, 611 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Davies, J. A. Organizing organoids: stem cells branch out. Cell Stem Cell 21, 705–706 (2017).

    Article  CAS  PubMed  Google Scholar 

  174. Wu, H. et al. Comparative analysis and refinement of human PSC-derived kidney organoid differentiation with single-cell transcriptomics. Cell Stem Cell 23, 869–881 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Wilson, S. B. et al. Classification of indeterminate and off-target cell types within human kidney organoid differentiation. Preprint at bioRxiv https://doi.org/10.1101/2025.05.16.654519 (2025).

  176. Chen, A. X. et al. Controlled apoptosis of stromal cells to engineer human microlivers. Adv. Funct. Mater. 30, 1910442 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Loza, O. et al. A synthetic planar cell polarity system reveals localized feedback on FAT4–DS1 complexes. eLife 6, e24820 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Munro, D. A. D. & Davies, J. A. Vascularizing the kidney in the embryo and organoid: questioning assumptions about renal vasculogenesis. J. Am. Soc. Nephrol. 29, 1593–1595 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Honeycutt, S. E. et al. Netrin 1 directs vascular patterning and maturity in the developing kidney. Development 150, dev201886 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Luo, P. M., Gu, X., Chaney, C., Carroll, T. & Cleaver, O. Stromal netrin 1 coordinates renal arteriogenesis and mural cell differentiation. Development 150, dev201884 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Munro, D. A. D., Hohenstein, P. & Davies, J. A. Cycles of vascular plexus formation within the nephrogenic zone of the developing mouse kidney. Sci. Rep. 7, 3273 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Ryan, A. R. et al. Vascular deficiencies in renal organoids and ex vivo kidney organogenesis. Dev. Biol. 477, 98–116 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Maggiore, J. C. et al. A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells. Kidney Int. 106, 1086–1100 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Miao, Y. et al. Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids. Cell 188, 4295–4313 (2025).

    Article  CAS  PubMed  Google Scholar 

  185. Kroll, K. T. et al. A perfusable, vascularized kidney organoid-on-chip model. Biofabrication 16, 045003 (2024).

    Article  CAS  Google Scholar 

  186. Homan, K. A. et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat. Methods 16, 255–262 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. van den Berg, C. W. et al. Renal subcapsular transplantation of PSC-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation in vivo. Stem Cell Reports 10, 751–765 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  188. van den Berg, C. W., Koudijs, A., Ritsma, L. & Rabelink, T. J. In vivo assessment of size-selective glomerular sieving in transplanted human induced pluripotent stem cell-derived kidney organoids. J. Am. Soc. Nephrol. 31, 921–929 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Bantounas, I. et al. Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors. Stem Cell Reports 10, 766–779 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  190. Sallam, M. & Davies, J. Connection of ES cell-derived collecting ducts and ureter-like structures to host kidneys in culture. Organogenesis 17, 40–49 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Fusco, A. N., Oxburgh, L. & Carroll, T. J. The kidney stroma in development and disease. Nat. Rev. Nephrol. 21, 756–777 (2025).

    Article  PubMed  Google Scholar 

  192. Schnell, J. et al. Controlling nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity. Nat. Commun. 16, 8136 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Huang, B. et al. Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling. Cell Stem Cell 32, 1614–1633 (2025).

    Article  CAS  PubMed  Google Scholar 

  194. Tran, T. et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell Stem Cell 29, 1083–1101 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Cruz, N. M. et al. Modelling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia. Nat. Biomed. Eng. 6, 463–475 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Majumdar, A., Vainio, S., Kispert, A., McMahon, J. & McMahon, A. P. Wnt11 and RET/GDNF pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130, 3175–3185 (2003).

    Article  CAS  PubMed  Google Scholar 

  197. Gottschalk, C. W. & Mylle, M. Evidence that the mammalian nephron functions as a countercurrent multiplier system. Science 128, 594 (1958).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank L. Prahl for helpful suggestions. This work was supported by NIH National Institute of General Medical Sciences Maximizing Investigators’ Research Award R35GM133380, NIH National Institute of Diabetes and Digestive and Kidney Diseases R01DK132296, NIDDK R01DK140070 and National Science Foundation CAREER award 2047271 (A.J.H.).

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  1. These authors contributed equally: Emma Warrner, Aria Zheyuan Huang.

Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

    Emma Warrner, Aria Zheyuan Huang & Alex J. Hughes

  2. Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA

    Emma Warrner, Aria Zheyuan Huang & Alex J. Hughes

  3. Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA

    Aria Zheyuan Huang

  4. Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA, USA

    Alex J. Hughes

  5. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Alex J. Hughes

  6. Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Alex J. Hughes

  7. Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Alex J. Hughes

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E.W., A.Z.H. and A.J.H. conceptualized the Review, designed figures and wrote and revised the manuscript.

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Warrner, E., Huang, A.Z. & Hughes, A.J. Developmentally inspired synthetic kidney engineering. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-026-03011-9

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