Defining the identity of mouse embryonic dermal fibroblasts.
Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown. Here we applied Shannon entropy analysis to identify the gene expression signature of mouse embryonic dermal fibroblasts. We used available human DNase-seq and histone modification ChiP-seq data on various cell-types to demonstrate that genes in the fibroblast cell identity signature can be epigenetically repressed in other cell-types. We found a subset of the signature genes whose expression is dependent on Wnt/β-catenin activity in vivo. With our approach, we have defined and validated a statistically derived gene expression signature that may mediate dermal fibroblast identity and function in development and disease. genesis 54:415-430, 2016. © 2016 Wiley Periodicals, Inc.
Department of Biology, Case Western Reserve University, Cleveland, Ohio.
Isadore
I
Budnick
Department of Biology, Case Western Reserve University, Cleveland, Ohio.
Emily
E
Hamburg-Shields
Department of Biology, Case Western Reserve University, Cleveland, Ohio.
Demeng
D
Chen
Epithelial Biology Program, Department of Dermatology, Stanford University, California.
Eduardo
E
Torre
Department of Biology, Case Western Reserve University, Cleveland, Ohio.
Andrew
A
Jarrell
Department of Pharmaceutical Sciences, University of California, Irvine, California.
Batool
B
Akhtar-Zaidi
Department of Pharmaceutical Sciences, University of California, Irvine, California.
Olivia
O
Cordovan
Epithelial Biology Program, Department of Dermatology, Stanford University, California.|Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.
Rob C
RC
Spitale
Department of Pharmaceutical Sciences, University of California, Irvine, California.
Peter
P
Scacheri
Department of Biology, Case Western Reserve University, Cleveland, Ohio.|Department of Pharmaceutical Sciences, University of California, Irvine, California.|Department of Dermatology, Case Western Reserve University, Cleveland, Ohio.
Radhika P
RP
Atit
D000818:Animals; D002454:Cell Differentiation; D020405:Dermis / Q000166:cytology* / Q000196:embryology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D059467:Transcriptome; D060449:Wnt Signaling Pathway / Q000235:genetics*
dermis; fate specification; genomics; hair; transcription