High Runx1 levels promote a reversible more differentiated cell-state in hair follicle stem cells during quiescence
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ABSTRACT: Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation 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 implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation 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. Freshly isolated skin cells were FACS sorted based on K15-GFP+/a6-integrin+/CD34- as hair germ and K15-GFP+/a6-integrin+/CD34+ bulge cells. Duplicate samlpes from mice at PD20 that showed telogen morphology throughout skin were used for RNA prepartion and Affymetrix analysis. Wild and transgenic samples after 1-day of doxycycline treatement were compared.
ORGANISM(S): Mus musculus
SUBMITTER: Tudorita Tumbar
PROVIDER: E-GEOD-53077 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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