Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice
Zhuzhen Zhang, … , Rana K. Gupta, Philipp E. Scherer
Zhuzhen Zhang, … , Rana K. Gupta, Philipp E. Scherer
Published September 10, 2019
Citation Information: J Clin Invest. 2019;129(12):5327-5342. https://doi.org/10.1172/JCI130239.
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Research Article Dermatology Metabolism

Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice

Abstract

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear. Here, we isolated dermal adipocytes and characterized dermal fat at the cellular and molecular level. Together with dWAT’s dynamic responses to external stimuli, we established that dermal adipocytes are a distinct class of white adipocytes with high plasticity. By combining pulse-chase lineage tracing and single-cell RNA sequencing, we observed that mature dermal adipocytes undergo dedifferentiation and redifferentiation under physiological and pathophysiological conditions. Upon various challenges, the dedifferentiated cells proliferate and redifferentiate into adipocytes. In addition, manipulation of dWAT highlighted an important role for mature dermal adipocytes for hair cycling and wound healing. Altogether, these observations unravel a surprising plasticity of dermal adipocytes and provide an explanation for the dynamic changes in dWAT mass that occur under physiological and pathophysiological conditions, and highlight the important contributions of dWAT toward maintaining skin homeostasis.

Authors

Zhuzhen Zhang, Mengle Shao, Chelsea Hepler, Zhenzhen Zi, Shangang Zhao, Yu A. An, Yi Zhu, Alexandra L. Ghaben, May-yun Wang, Na Li, Toshiharu Onodera, Nolwenn Joffin, Clair Crewe, Qingzhang Zhu, Lavanya Vishvanath, Ashwani Kumar, Chao Xing, Qiong A. Wang, Laurent Gautron, Yingfeng Deng, Ruth Gordillo, Ilja Kruglikov, Christine M. Kusminski, Rana K. Gupta, Philipp E. Scherer

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Figure 2

Transcriptional profiling of dWAT during hair cycling.

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Transcriptional profiling of dWAT during hair cycling. (A) Venn diagram ...
(A) Venn diagram of genes expressed in dermal adipocytes harvested from 21-, 25-, 29-, 35-, and 49-day-old male mice, referred to as P21, P25, P29, P35, and P49. The coexpressed or uniquely expressed genes are visually presented. Default threshold of FPKM value for RNA-Seq is set to 1. Each group contained 3 samples; each sample contained dermal adipocytes harvested from 6 mice. (B) Principal component analysis of transcriptome of all samples. For all the data, 1 sample from D25 was excluded as it was clustered between P21 and P25. (C) Hierarchical clustering of transcriptional profile of P21, P25, P29, P35, and P49 dermal adipocytes. One cluster with enriched genes in anagen relative to catagen and telogen was defined as set I; one cluster with decreased genes in anagen relative to catagen and telogen was defined as set II. FC, fold change. (D and E) Gene ontology (GO) analysis of gene set I and set II. (F–J) Expression level of genes related to adipogenesis (F), Camp gene (G), Wnt family members (H), genes related to lipolysis and oxidation (I), Bmp family members, and Noggin (J) in dermal adipocytes during hair cycling. (K) Heatmap of collagen gene expression during hair cycling. One-way ANOVA with Dunnett’s test. A P value less than 0.05 is considered significant. *P < 0.05, **P < 0.01.