title: BMP signaling and its pSMAD1/5 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.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Genander
authors.affiliation: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cook
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Ludwig Institute for Cancer Research, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramsköld
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Brice E
authors.initials: BE
authors.lastname: Keyes
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Mertz
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Ludwig Institute for Cancer Research, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.affiliation: 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.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D019070:Cell Lineage; D053263:Gene Regulatory Networks; D018859:Hair Follicle / Q000166:cytology*; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism*; D051902:Smad5 Protein / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D051796:Inhibitor of Differentiation Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein