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Free keywords:
Animals
*Cell Differentiation/genetics
*Cell Lineage/genetics
Cell Physiological Phenomena
*Cell Plasticity/genetics
Humans
Signal Transduction/genetics/*physiology
Stem Cell Niche/genetics/*physiology
*Epithelium
*Intestine
*Lung
*Niche
*Skin
*Stem cells
Abstract:
Stem cells have the ability to self-renew and differentiate along multiple lineages, driving tissue homeostasis and regeneration. Paradigms of unidirectional, hierarchical differentiation trajectories observed in embryonic and hematopoietic stem cells have traditionally been applied to tissue-resident stem cells. However, accumulating evidence implicates stemness as a bidirectional, dynamic state that is largely governed by the niche, which facilitates plasticity and adaptability to changing conditions. In this Review, we discuss mechanisms of cell fate regulation through niche-derived cues, with a particular focus on epithelial stem cells of the mammalian skin, intestine and lung. We discuss a spectrum of niche-derived biochemical, mechanical and architectural inputs that define stem cell states during morphogenesis, homeostasis and regeneration, and highlight how these diverse inputs influence stem cell plasticity.
