Spatial organization within a niche as a determinant of stem-cell fate

Stem-cell niches in mammalian tissues are often heterogeneous and compartmentalized; however, whether distinct niche locations determine different stem-cell fates remains unclear. To test this hypothesis, here we use the mouse hair follicle niche and combine intravital microscopy with genetic lineage tracing to re-visit the same stem-cell lineages, from their exact place of origin, throughout regeneration in live mice. Using this method, we show directly that the position of a stem cell within the hair follicle niche can predict whether it is likely to remain uncommitted, generate precursors or commit to a differentiated fate. Furthermore, using laser ablation we demonstrate that hair follicle stem cells are dispensable for regeneration, and that epithelial cells, which do not normally participate in hair growth, re-populate the lost stem-cell compartment and sustain hair regeneration. This study provides a general model for niche-induced fate determination in adult tissues. By combining lineage tracing with intravital microscopy, the position of a stem cell within its extended mouse hair follicle niche is shown to control its long-term fate and behaviour; laser ablation to remove restricted cell populations shows that bulge stem cells are dispensable for hair regeneration, and non-hair epithelial cells may change their fate to compensate and sustain hair growth. Niche location key to stem-cell fate By combining live imaging and single stem cell/progeny labelling in live mice, Valentina Greco and colleagues show that cells located in different compartments of the hair follicle stem-cell niche have different cell fates. Laser ablation shows that multipotent bulge stem cells, central to hair follicle development, are not essential for hair regeneration because epithelial cells can re-populate the lost stem-cell compartment. These findings demonstrate that the position of a stem cell within its extended niche controls its long-term fate and behaviour. This may be a general mechanism for the regulation of other adult stem cells.