title: Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
abstract: Increasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with "stemness." Of these, miR-125b is dramatically downregulated in early SC progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC progenies, tissue balance is reversibly skewed toward stemness at the expense of epidermal, oil-gland, and HF differentiation. Using gain- and loss-of-function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA. fuchslb@rockefeller.edu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Nicole
authors.initials: N
authors.lastname: Stokes
authors.forename: Lisa
authors.initials: L
authors.lastname: Polak
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation; D017124:Conserved Sequence / Q000235:genetics; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006197:Hair / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D010641:Phenotype; D000074462:Positive Regulatory Domain I-Binding Factor 1; D018167:Receptors, Calcitriol / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C513258:Prdm1 protein, mouse; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1