The expanding landscape of adult stem cell niches

Adult stem cells reside within specialized niches that provide the local instructions needed to sustain regenerative fitness. Since the recognition that stem cells are not autonomous, the concept of the niche has widened from a local collection of supportive cells into a landscape of combinatorial microenvironments that stem cells help build rather than simply inhabit. Advances in molecular, genetic and deep imaging approaches and engineered organoid systems have shown these microenvironments to be far more diverse and dynamic than once appreciated. In this review, we consider how diverse cellular components build the stem cell niche across tissues, and how a growing set of non-cellular factors, from mechanical forces to metabolites, work alongside them to govern stem cell fate and regenerative capacity. We then ask how combinatorial niche interactions, spatial organization and reciprocal communication with stem cells support the diverse functions stem cells carry out across the lifespan. Understanding the niche as a dynamic and evolving system, rather than a fixed anatomical unit, promises insight into the fundamental mechanisms of developmental, regenerative, and pathologic stem cell function, with substantial implications for regenerative medicine.