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PMID: 21549329 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells.

Cell stem cell ·Vol. 8 ·No. 5 ·2011-05-06 ·Pages 552-65

Brownell I, Guevara E, Bai CB, Loomis CA, Joyner AL

Abstract

In adult skin, stem cells in the hair follicle bulge cyclically regenerate the follicle, whereas a distinct stem cell population maintains the epidermis. The degree to which all bulge cells have equal regenerative potential is not known. We found that Sonic hedgehog (Shh) from neurons signals to a population of cells in the telogen bulge marked by the Hedgehog response gene Gli1. Gli1-expressing bulge cells function as multipotent stem cells in their native environment and repeatedly regenerate the anagen follicle. Shh-responding perineural bulge cells incorporate into healing skin wounds where, notably, they can change their lineage into epidermal stem cells. The perineural niche (including Shh) is dispensable for follicle contributions to acute wound healing and skin homeostasis, but is necessary to maintain bulge cells capable of becoming epidermal stem cells. Thus, nerves cultivate a microenvironment where Shh creates a molecularly and phenotypically distinct population of hair follicle stem cells.

MeSH Terms
Adult Stem Cells/cytology,metabolism Animals Animals, Genetically Modified Cell Lineage Cell Survival Cell Transdifferentiation Cells, Cultured Epidermis/injuries,physiology Gene Expression Regulation Gene Knock-In Techniques Hair Follicle/cytology,physiology Hedgehog Proteins/metabolism Mice Multipotent Stem Cells/cytology,metabolism Neurons/cytology,physiology Oncogene Proteins/genetics,metabolism Regeneration Stem Cell Niche Trans-Activators/genetics,metabolism Transgenes/genetics Wound Healing Zinc Finger Protein GLI1
Chemicals
Hedgehog Proteins Oncogene Proteins Trans-Activators Zinc Finger Protein GLI1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Brownell Isaac
Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Guevara Elizabeth
Bai C Brian
Loomis Cynthia A
Joyner Alexandra L
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2011.02.021
Published
2011-05-06
Pages
552-65
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC3089905
Subset
IM
Grants
NCI NIH HHS · R01 CA128158-11 · United States
NCI NIH HHS · R01 CA128158 · United States
NIAMS NIH HHS · F32 AR055435 · United States
NIAMS NIH HHS · F32AR55435 · United States
NCI NIH HHS · R01 CA128158-12 · United States
NCI NIH HHS · R01CA128158 · United States
NCI NIH HHS · R01 CA128158-13 · United States
NCI NIH HHS · R01 CA128158-14 · United States
Databases
GEO
GSE28108
Corrections
CommentIn
PMID: 21549317
External Links
PubMed source DOI: 10.1016/j.stem.2011.02.021 PMC Full Text View journal details
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