High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying matrix cells. EPs can revert to SCs upon injury, but whether this dedifferentiation occurs in normal HF homeostasis (hair cycle) and the mechanisms regulating both differentiation and dedifferentiation are unclear. Here, we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression induces hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome toward a cell state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and dedifferentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Song Eun
SE
Lee
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Aiko
A
Sada
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Meng
M
Zhang
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
David J
DJ
McDermitt
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Shu Yang
SY
Lu
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Kenneth J
KJ
Kemphues
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: tt252@cornell.edu.
Tudorita
T
Tumbar
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors
D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D013752:Tetracycline