Universität zu Köln

Kloepper, Jennifer E., Baris, Olivier R., Reuter, Karen, Kobayashi, Ken, Weiland, Daniela, Vidali, Silvia ORCID: 0000-0003-1981-8833, Tobin, Desmond J., Niemann, Catherin, Wiesner, Rudolf J. and Paus, Ralf ORCID: 0000-0002-3492-9358 (2015). Mitochondrial Function in Murine Skin Epithelium Is Crucial for Hair Follicle Morphogenesis and Epithelial-Mesenchymal Interactions. J. Invest. Dermatol., 135 (3). S. 679 - 690. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1523-1747

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Abstract

Here, we studied how epithelial energy metabolism impacts overall skin development by selectively deleting intraepithelial mtDNA in mice by ablating a key maintenance factor (Tfam(EKO)), which induces loss of function of the electron transport chain (ETC). Quantitative (immuno)histomorphometry demonstrated that Tfam(EKO) mice showed significantly reduced hair follicle (HF) density and morphogenesis, fewer intrafollicular keratin15+ epithelial progenitor cells, increased apoptosis, and reduced proliferation. Tfam(EKO) mice also displayed premature entry into (aborted) HF cycling by apoptosis-driven HF regression (catagen). Ultrastructurally, Tfam(EKO) mice exhibited severe HF dystrophy, pigmentary abnormalities, and telogen-like condensed dermal papillae. Epithelial HF progenitor cell differentiation (Plet1, Lrig1 Lef1and beta-catenin), sebaceous gland development (adipophilin, Scd1, and oil red), and key mediators/markers of epithelial mesenchymal interactions during skin morphogenesis (NCAM, versican, and alkaline phosphatase) were all severely altered in Tfam(EKO) mice. Moreover, the number of mast cells, major histocompatibility complex class II+, or CD11b+ immunocytes in the skin mesenchyme was increased, and essentially no subcutis developed. Therefore, in contrast to their epidermal counterparts, pilosebaceous unit stem cells depend on a functional ETC. Most importantly, our findings point toward a frontier in skin biology: the coupling of HF keratinocyte mitochondrial function with the epithelial-mesenchymal interactions that drive overall development of the skin and its appendages.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kloepper, Jennifer E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reuter, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Kobayashi, Ken UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiland, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Vidali, Silvia UNSPECIFIED orcid.org/0000-0003-1981-8833 UNSPECIFIED Tobin, Desmond J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemann, Catherin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paus, Ralf UNSPECIFIED orcid.org/0000-0002-3492-9358 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-411439
DOI:	10.1038/jid.2014.475
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	135
Number:	3
Page Range:	S. 679 - 690
Date:	2015
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STEM-CELLS; HEMATOPOIETIC STEM; INDUCED ALOPECIA; DNA MUTATIONS; MICE; DIFFERENTIATION; EPIDERMIS; CYCLOPHOSPHAMIDE; PROLIFERATION; PIGMENTATION Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41143