JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin

Nature Communications
Karmveer SinghKarin Scharffetter-Kochanek

Abstract

Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile. A fate switch occurs in a subset of JunB deficient epidermal progenitors during wound healing resulting in de novo formation of sebaceous glands. Dysregulated Notch signaling is identified to be causal for this phenotype. In fact, pharmacological inhibition of Notch signaling can efficiently restore the lineage drift, impaired epidermal differentiation and disrupted barrier function in JunB conditional knockout mice. These findings define an unprecedented role for JunB in epidermal-pilosebaceous stem cell homeostasis and its pathology.

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Citations

Jul 17, 2019·Experimental Dermatology·Tongyu C WikramanayakeRalf Paus
Oct 22, 2020·Nature Communications·Bénédicte OulèsFiona M Watt
Jul 10, 2021·Journal of Dermatological Science·Sayaka Shibata
Jul 3, 2021·Journal of Cosmetic Dermatology·Fernanda Ayres de Morais E Silva CardosoAdilson da Costa
Nov 23, 2021·The Journal of Investigative Dermatology·Karmveer SinghKarin Scharffetter-Kochanek

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Datasets Mentioned

BETA
GSE89928

Methods Mentioned

BETA
biopsies
FACS
biopsy
RNA-seq
PCR
Profiler
immunoprecipitations
ChIP

Software Mentioned

RWeblogo
Cufflinks
HISAT2
Mass Hunter
Homer
samtools
Picards
FASTX
TRANSFAC
RStudio

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