4.8 Article

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

Journal

NATURE
Volume 502, Issue 7472, Pages 513-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nature12602

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Funding

  1. New York Stem Cell Foundation
  2. American Cancer Society [RGS-12-059-01-DCC]
  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases [1RO1AR063663-01]

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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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