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Cell Stem Cell. 2014 Nov 6;15(5):619-33. doi: 10.1016/j.stem.2014.09.009. Epub 2014 Oct 9.

BMP signaling and its pSMAD1/5 target genes differentially regulate hair follicle stem cell lineages.

Author information

1
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2
Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
3
Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Ludwig Institute for Cancer Research, Karolinska Institutet, 171 77 Stockholm, Sweden.
4
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.

Abstract

Hair follicle stem cells (HFSCs) and their transit amplifying cell (TAC) progeny sense BMPs at defined stages of the hair cycle to control their proliferation and differentiation. Here, we exploit the distinct spatial and temporal localizations of these cells to selectively ablate BMP signaling in each compartment and examine its functional role. We find that BMP signaling is required for HFSC quiescence and to promote TAC differentiation along different lineages as the hair cycle progresses. We also combine in vivo genome-wide chromatin immunoprecipitation and deep-sequencing, transcriptional profiling, and loss-of-function genetics to define BMP-regulated genes. We show that some pSMAD1/5 targets, like Gata3, function specifically in TAC lineage-progression. Others, like Id1 and Id3, function in both HFSCs and TACs, but in distinct ways. Our study therefore illustrates the complex differential roles that a key signaling pathway can play in regulation of closely related stem/progenitor cells within the context of their overall niche.

PMID:
25312496
PMCID:
PMC4276600
DOI:
10.1016/j.stem.2014.09.009
[Indexed for MEDLINE]
Free PMC Article

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