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Nature. 2013 Oct 24;502(7472):513-8. doi: 10.1038/nature12602. Epub 2013 Oct 6.

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

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Department of Genetics, Department of Dermatology, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.


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.

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