Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice

Cell Death & Differentiation (2026)Cite this article

Subjects

Abstract

Histone methyltransferase SETD2 is recurrently mutated in hematopoietic malignancies. Our previous study showed that Setd2 deficiency impairs the self-renewal potential of murine hematopoietic stem cells (HSCs) and drives myelodysplastic syndrome (MDS)-like disorders. However, the precise oncogenic advantages conferred upon HSCs by Setd2 loss remain unclear. In this study, we found that Setd2 deficiency disrupted the fidelity of HSC lineage differentiation with preferential erythroid commitment and excessive macrophage priming, leading to ineffective erythropoiesis and the production of inflammatory embryonic-derived Kupffer cell (EmKC)-like cells. Notably, these EmKC-like cells exhibited HSC-independent self-renewal capability and remotely perturbed intramedullary hematopoiesis by inducing systemic inflammation. Furthermore, macrophage depletion effectively alleviated the inflammatory state and relieved MDS-like symptoms. Mechanistically, Setd2 loss leads to significant changes in DNA methylation and chromatin accessibility, resulting in the activation of Irf8. These findings suggest that the long-lived inflammatory cells may compensate for the HSC self-renewal defects, triggering systemic inflammation and driving hematopoietic malignant transformation. This paradigm provides a new understanding of hematopoietic malignancies with functional defects and exhaustion of HSCs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Comparative pathogenic signatures of Setd2 deficiency-associated disease subtypes.
Fig. 2: MDS-like phenotype due to Setd2 loss is transplantable.
Fig. 3: Liver EmKC-like cells are capable of reconstituting MDS-like disorder.
Fig. 4: Macrophage depletion alleviates MDS-like symptoms in Setd2-KO mice.
Fig. 5: EmKC-like cells orchestrate systemic inflammation in MDS-like mice.
Fig. 6: Setd2 loss induces erythroid and myeloid lineage priming in HSCs.
Fig. 7: Setd2 deficiency influences the expression and activity of Irf8 by disturbing chromatin accessibility and DNA methylation in HSPCs.

Similar content being viewed by others

Data availability

All raw and processed data from scRNA-seq, bulk RNA-seq, ATAC-seq, and WGBS are available in the National Omics Data Encyclopedia (NODE) under Access number: OEP004811. The RNA-seq of BM LSKs from old WT and KO-MDS mice have been previously published (GEO: GSE108617). Source data are provided with this paper. The detailed experimental procedures and analytical methodologies are provided in the Supplementary Information.

References

  1. Issa JP. The myelodysplastic syndrome as a prototypical epigenetic disease. Blood. 2013;121:3811–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017;17:5–19.

    Article  PubMed  CAS  Google Scholar 

  3. Kristinsson SY, Bjorkholm M, Hultcrantz M, Derolf AR, Landgren O, Goldin LR. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J Clin Oncol. 2011;29:2897–903.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sallman DA, List A. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood. 2019;133:1039–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Barreyro L, Chlon TM, Starczynowski DT. Chronic immune response dysregulation in MDS pathogenesis. Blood. 2018;132:1553–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ganan-Gomez I, Wei Y, Starczynowski DT, Colla S, Yang H, Cabrero-Calvo M, et al. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia. 2015;29:1458–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Varney ME, Melgar K, Niederkorn M, Smith M, Barreyro L, Starczynowski DT. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp Hematol. 2015;43:587–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Basiorka AA, McGraw KL, Eksioglu EA, Chen X, Johnson J, Zhang L, et al. The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype. Blood. 2016;128:2960–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 2016;19:613–27.

    Article  PubMed  CAS  Google Scholar 

  11. Chen X, Eksioglu EA, Zhou J, Zhang L, Djeu J, Fortenbery N, et al. Induction of myelodysplasia by myeloid-derived suppressor cells. J Clin Invest. 2013;123:4595–611.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Schneider RK, Schenone M, Ferreira MV, Kramann R, Joyce CE, Hartigan C, et al. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nat Med. 2016;22:288–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Ribezzo F, Snoeren IAM, Ziegler S, Stoelben J, Olofsen PA, Henic A, et al. Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome. Leukemia. 2019;33:1759–72.

    Article  PubMed  CAS  Google Scholar 

  14. Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature. 2015;518:547–51.

    Article  PubMed  Google Scholar 

  15. Hoeffel G, Chen J, Lavin Y, Low D, Almeida FF, See P, et al. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity. 2015;42:665–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Guilliams M, Scott CL. Liver macrophages in health and disease. Immunity. 2022;55:1515–29.

    Article  PubMed  CAS  Google Scholar 

  17. Scott CL, Zheng F, De Baetselier P, Martens L, Saeys Y, De Prijck S, et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun. 2016;7:10321.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Li W, Yang Y, Yang L, Chang N, Li L. Monocyte-derived Kupffer cells dominate in the Kupffer cell pool during liver injury. Cell Rep. 2023;42:113164.

    Article  PubMed  CAS  Google Scholar 

  19. Tran S, Baba I, Poupel L, Dussaud S, Moreau M, Gelineau A, et al. Impaired Kupffer cell self-renewal alters the liver response to lipid overload during non-alcoholic steatohepatitis. Immunity. 2020;53:627–40.e5.

    Article  PubMed  CAS  Google Scholar 

  20. Seidman JS, Troutman TD, Sakai M, Gola A, Spann NJ, Bennett H, et al. Niche-specific reprogramming of epigenetic landscapes drives myeloid cell diversity in nonalcoholic steatohepatitis. Immunity. 2020;52:1057–74.e7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Remmerie A, Martens L, Thone T, Castoldi A, Seurinck R, Pavie B, et al. Osteopontin expression identifies a subset of recruited macrophages distinct from Kupffer cells in the fatty liver. Immunity. 2020;53:641–57.e14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Fan N, Lavu S, Hanson CA, Tefferi A. Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients. Blood Cancer J. 2018;8:119.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, et al. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005;280:35261–71.

    Article  PubMed  CAS  Google Scholar 

  24. Hu M, Sun XJ, Zhang YL, Kuang Y, Hu CQ, Wu WL, et al. Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proc Natl Acad Sci USA. 2010;107:2956–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL, Strahl BD. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol Cell Biol. 2005;25:3305–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L, Krebs AR, et al. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 2015;520:243–7.

    Article  PubMed  CAS  Google Scholar 

  27. Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, et al. Histone H3 trimethylation at lysine 36 guides m(6)A RNA modification co-transcriptionally. Nature. 2019;567:414–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science. 2010;327:996–1000.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Wen H, Li Y, Xi Y, Jiang S, Stratton S, Peng D, et al. ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature. 2014;508:263–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Li F, Mao G, Tong D, Huang J, Gu L, Yang W, et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha. Cell. 2013;153:590–600.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Pfister SX, Ahrabi S, Zalmas LP, Sarkar S, Aymard F, Bachrati CZ, et al. SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability. Cell Rep. 2014;7:2006–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Chen K, Liu J, Liu S, Xia M, Zhang X, Han D, et al. Methyltransferase SETD2-mediated methylation of STAT1 is critical for interferon antiviral activity. Cell. 2017;170:492–506.e14.

    Article  PubMed  CAS  Google Scholar 

  33. Park IY, Powell RT, Tripathi DN, Dere R, Ho TH, Blasius TL, et al. Dual chromatin and cytoskeletal remodeling by SETD2. Cell. 2016;166:950–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Yuan H, Han Y, Wang X, Li N, Liu Q, Yin Y, et al. SETD2 restricts prostate cancer metastasis by integrating EZH2 and AMPK signaling pathways. Cancer Cell. 2020;38:350–65.e7.

    Article  PubMed  CAS  Google Scholar 

  35. Lu M, Zhao B, Liu M, Wu L, Li Y, Zhai Y, et al. Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy. NPJ Precis Oncol. 2021;5:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. McKinney M, Moffitt AB, Gaulard P, Travert M, De Leval L, Nicolae A, et al. The genetic basis of hepatosplenic T-cell lymphoma. Cancer Discov. 2017;7:369–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Mar BG, Bullinger LB, McLean KM, Grauman PV, Harris MH, Stevenson K, et al. Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia. Nat Commun. 2014;5:3469.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhu X, He F, Zeng H, Ling S, Chen A, Wang Y, et al. Identification of functional cooperative mutations of SETD2 in human acute leukemia. Nat Genet. 2014;46:287–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Leung W, Teater M, Durmaz C, Meydan C, Chivu AG, Chadburn A, et al. SETD2 haploinsufficiency enhances germinal center-associated AICDA somatic hypermutation to drive B-cell lymphomagenesis. Cancer Discov. 2022;12:1782–803.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Parker H, Rose-Zerilli MJ, Larrayoz M, Clifford R, Edelmann J, Blakemore S, et al. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia. Leukemia. 2016;30:2179–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Li J, Peng Z, Luo F, Chen Y. SET domain containing 2 deficiency in myelodysplastic syndrome. Front Genet. 2020;11:794.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chen BY, Song J, Hu CL, Chen SB, Zhang Q, Xu CH, et al. SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS. Blood. 2020;135:2271–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Zhang YL, Sun JW, Xie YY, Zhou Y, Liu P, Song JC, et al. Setd2 deficiency impairs hematopoietic stem cell self-renewal and causes malignant transformation. Cell Res. 2018;28:476–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Zhou Y, Yan X, Feng X, Bu J, Dong Y, Lin P, et al. Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation. Haematologica. 2018;103:1110–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Chu SH, Chabon JR, Matovina CN, Minehart JC, Chen BR, Zhang J, et al. Loss of H3K36 methyltransferase SETD2 impairs V(D)J recombination during lymphoid development. iScience. 2020;23:100941.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Ji Z, Sheng Y, Miao J, Li X, Zhao H, Wang J, et al. The histone methyltransferase Setd2 is indispensable for V(D)J recombination. Nat Commun. 2019;10:3353.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ding Z, Cai T, Tang J, Sun H, Qi X, Zhang Y, et al. Setd2 supports GATA3(+)ST2(+) thymic-derived Treg cells and suppresses intestinal inflammation. Nat Commun. 2022;13:7468.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Liu Y, Pop R, Sadegh C, Brugnara C, Haase VH, Socolovsky M. Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo. Blood. 2006;108:123–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Shim YA, Campbell T, Weliwitigoda A, Dosanjh M, Johnson P. Regulation of CD71(+)TER119(+) erythroid progenitor cells by CD45. Exp Hematol. 2020;86:53–66.e1.

    Article  PubMed  CAS  Google Scholar 

  50. Mass E, Nimmerjahn F, Kierdorf K, Schlitzer A. Tissue-specific macrophages: how they develop and choreograph tissue biology. Nat Rev Immunol. 2023;23:563–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Barisas DAG, Choi K. Extramedullary hematopoiesis in cancer. Exp Mol Med. 2024;56:549–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Jiang K, Tian K, Yu Y, Wu E, Yang M, Pan F, et al. Kupffer cells determine intrahepatic traffic of PEGylated liposomal doxorubicin. Nat Commun. 2024;15:6136.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Liu J, Zhu Z, Leung GK. Erythrophagocytosis by microglia/macrophage in intracerebral hemorrhage: from mechanisms to translation. Front Cell Neurosci. 2022;16:818602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Soyfer EM, Fleischman AG. Myeloproliferative neoplasms - blurring the lines between cancer and chronic inflammatory disorder. Front Oncol. 2023;13:1208089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Rodriguez-Sevilla JJ, Colla S. Inflammation in myelodysplastic syndrome pathogenesis. Semin Hematol. 2024;61:385–96.

    Article  PubMed  Google Scholar 

  56. Stubbins RJ, Platzbecker U, Karsan A. Inflammation and myeloid malignancy: quenching the flame. Blood. 2022;140:1067–74.

    Article  PubMed  CAS  Google Scholar 

  57. Kesharwani P, Dash D, Koiri RK. Deciphering the role of hepcidin in iron metabolism and anemia management. J Trace Elem Med Biol. 2025;87:127591.

    Article  PubMed  CAS  Google Scholar 

  58. Sun Y, Tong H, Chu X, Li Y, Zhang J, Ding Y, et al. Notch1 regulates hepatic thrombopoietin production. Blood. 2024;143:2778–90.

    Article  PubMed  CAS  Google Scholar 

  59. Merz AMA, Platzbecker U. Treatment of lower-risk myelodysplastic syndromes. Haematologica. 2025;110:330–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  60. Gonzalez-Menendez P, Phadke I, Olive ME, Joly A, Papoin J, Yan H, et al. Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A. Blood. 2023;141:2520–36.

    PubMed  PubMed Central  CAS  Google Scholar 

  61. Mass, E, I Ballesteros, M Farlik, F Halbritter, P Gunther, L Crozet, et al. Specification of tissue-resident macrophages during organogenesis. Science. 2016;353:aaf4238.

  62. Simon JM, Hacker KE, Singh D, Brannon AR, Parker JS, Weiser M, et al. Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Res. 2014;24:241–50.

    Article  PubMed  CAS  Google Scholar 

  63. Xie Y, Sahin M, Sinha S, Wang Y, Nargund AM, Lyu Y, et al. SETD2 loss perturbs the kidney cancer epigenetic landscape to promote metastasis and engenders actionable dependencies on histone chaperone complexes. Nat Cancer. 2022;3:188–202.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Domcke S, Bardet AF, Adrian Ginno P, Hartl D, Burger L, Schubeler D. Competition between DNA methylation and transcription factors determines binding of NRF1. Nature. 2015;528:575–9.

    Article  PubMed  CAS  Google Scholar 

  65. Yin, Y, E Morgunova, A Jolma, E Kaasinen, B Sahu, S Khund-Sayeed, et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 2017;356:eaaj2239.

  66. Izzo F, Lee SC, Poran A, Chaligne R, Gaiti F, Gross B, et al. DNA methylation disruption reshapes the hematopoietic differentiation landscape. Nat Genet. 2020;52:378–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Guo Y, Xue Z, Yuan R, Li JJ, Pastor WA, Liu W. RAD: a web application to identify region associated differentially expressed genes. Bioinformatics. 2021;37:2741–3.

    Article  PubMed  CAS  Google Scholar 

  68. Wang L, You X, Ruan D, Shao R, Dai HQ, Shen W, et al. TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes. Nat Commun. 2022;13:4709.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Friedrich, C and O Kosmider. The mesenchymal niche in myelodysplastic syndromes. Diagnostics. 2022;12:1639.

  70. Kouroukli O, Symeonidis A, Foukas P, Maragkou MK, Kourea EP. Bone marrow immune microenvironment in myelodysplastic syndromes. Cancers. 2022;14:5656.

  71. Tanaka TN, Bejar R. MDS overlap disorders and diagnostic boundaries. Blood. 2019;133:1086–95.

    Article  PubMed  CAS  Google Scholar 

  72. Guryanova OA, Lieu YK, Garrett-Bakelman FE, Spitzer B, Glass JL, Shank K, et al. Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells. Leukemia. 2016;30:1133–42.

    Article  PubMed  CAS  Google Scholar 

  73. Kuhn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science. 1995;269:1427–9.

    Article  PubMed  CAS  Google Scholar 

  74. Georgiades P, Ogilvy S, Duval H, Licence DR, Charnock-Jones DS, Smith SK, et al. VavCre transgenic mice: a tool for mutagenesis in hematopoietic and endothelial lineages. Genesis. 2002;34:251–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was supported by National Natural Science Foundation of China (81870102, 82070150), the Young Scientists Fund of the National Natural Science Foundation of China (82400168), Natural Science Foundation of Shanghai Science and Technology Innovation Plan (23ZR1439700), Postdoctoral Fellowship Program of CPSF (GZC20241054), and Samuel Waxman Cancer Research Foundation.

Author information

Author notes

  1. These authors contributed equally: Jiachun Song, Fuhui Wang, Yinyin Xie.

Authors and Affiliations

  1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

    Jiachun Song, Fuhui Wang, Yinyin Xie, Xinyue Luo, Hong Tao, Rong Fan, Yan Zhou, Jing Wu, Ting Huang, Xiaojian Sun, Qiuhua Huang & Yuanliang Zhang

  2. Central Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

    Yan Zhou

  3. Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

    Haifeng Zhao

Authors
  1. Jiachun Song
    View author publications

    Search author on:PubMed Google Scholar

  2. Fuhui Wang
    View author publications

    Search author on:PubMed Google Scholar

  3. Yinyin Xie
    View author publications

    Search author on:PubMed Google Scholar

  4. Xinyue Luo
    View author publications

    Search author on:PubMed Google Scholar

  5. Hong Tao
    View author publications

    Search author on:PubMed Google Scholar

  6. Rong Fan
    View author publications

    Search author on:PubMed Google Scholar

  7. Yan Zhou
    View author publications

    Search author on:PubMed Google Scholar

  8. Jing Wu
    View author publications

    Search author on:PubMed Google Scholar

  9. Ting Huang
    View author publications

    Search author on:PubMed Google Scholar

  10. Haifeng Zhao
    View author publications

    Search author on:PubMed Google Scholar

  11. Xiaojian Sun
    View author publications

    Search author on:PubMed Google Scholar

  12. Qiuhua Huang
    View author publications

    Search author on:PubMed Google Scholar

  13. Yuanliang Zhang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

YLZ, QHH and XJS designed the research. YLZ, JCS, FHW, YYX, XYL, and HT performed experiments. YLZ, JCS and HFZ performed bioinformatics analysis. YLZ, JCS, FHW, YYX, XYL, HT, RF, YZ, JW, TH, HFZ, XJS, and QHH analyzed and discussed data. YLZ, JCS, and QHH wrote the manuscript.

Corresponding authors

Correspondence to Xiaojian Sun, Qiuhua Huang or Yuanliang Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, J., Wang, F., Xie, Y. et al. Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice. Cell Death Differ (2026). https://doi.org/10.1038/s41418-026-01715-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41418-026-01715-8

Search

Advanced search

Quick links