BMP signaling and its pSMADS1/5 target genes differentially regulate hair follicle stem cell lineages Journal Article
| Authors: | Genander, M.; Cook, P. J.; Ramsköld, D.; Keyes, B. E.; Mertz, A. F.; Sandberg, R.; Fuchs, E. |
| Article Title: | BMP signaling and its pSMADS1/5 target genes differentially regulate hair follicle stem cell lineages |
| 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. |
| Keywords: | signal transduction; controlled study; protein expression; nonhuman; protein function; cell proliferation; animal cell; mouse; transcription factor gata 3; bone morphogenetic protein; inhibitor of differentiation 1; smad1 protein; smad5 protein; protein targeting; transcription initiation; cell renewal; cell differentiation; cell population; immunoreactivity; cell lineage; stem cell; extracellular matrix; regulatory mechanism; nucleotide sequence; progeny; noggin; inhibitor of differentiation 2; beta catenin; fluorescence activated cell sorting; lymphoid enhancer factor 1; enhancer region; inhibitor of differentiation 3; hair follicle; hair root; transcription factor sox9; hair follicle stem cell; transcription factor runx2; wnt signaling pathway; priority journal; article; transcription factor msx1 |
| Journal Title: | Cell Stem Cell |
| Volume: | 15 |
| Issue: | 5 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2014-11-06 |
| Start Page: | 619 |
| End Page: | 633 |
| Language: | English |
| DOI: | 10.1016/j.stem.2014.09.009 |
| PROVIDER: | scopus |
| PMCID: | PMC4276600 |
| PUBMED: | 25312496 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
