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Stem cells

Like water on rock, the microenvironment bends stem cell fate

Nature Reviews Molecular Cell Biology volume 27, page 177 (2026)Cite this article

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Development has long been viewed as a process confined to embryogenesis, a transient window during which cells acquire their identities and long-lived stem cells are established to sustain organ function. In adulthood, these tissue-resident stem cells were thought to be restricted to lineage-specific programs of self-renewal and differentiation, accurately regenerating their own family of progeny. A landmark study by Ito et al. in 2007 challenged this view, demonstrating that development does not end with birth but continues throughout life, rebuilding tissues in unexpected ways.

We tend to think about cellular reprogramming as the forced redirection of fate driven by a defined set of transcription factors. In their work, Ito et al. showed that reprogramming can arise naturally, enabling cells to assume new fate trajectories in response to microenvironmental pressures, supported by WNT-driven programs. This paper is one I consistently return to when teaching about the beauty of stem cells and the importance of the microenvironment (‘niches’) in driving stem cell function. Ito et al. revealed that adult epithelial identity can be rewritten, and like water shaping stone, the niche leaves its imprint, bending cell fate to meet the needs of the tissue.

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References

Original article

  • Ito, M. et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447, 316–320 (2007)

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  1. Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, CA, USA

    Shiri Gur-Cohen

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  1. Shiri Gur-Cohen
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Correspondence to Shiri Gur-Cohen.

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The author declares no competing interests.

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Gur-Cohen, S. Like water on rock, the microenvironment bends stem cell fate. Nat Rev Mol Cell Biol 27, 177 (2026). https://doi.org/10.1038/s41580-025-00935-z

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