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 1

dWAT is a fat depot with a unique identity.

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dWAT is a fat depot with a unique identity. (A) Schematic diagram of dWA...
(A) Schematic diagram of dWAT oscillation in mouse skin. (B) Graphic illustration of isolation of dermal adipocytes with floating digestion and floating centrifuge. (C) Differential gene expression analysis of the RNA-Seq results. Genes that changed less than 2-fold are represented with black dots. cpm, counts per million. (D–F) Reverse transcriptase PCR (RT-PCR) measurements of mRNA levels of general adipocyte marker genes (D), brown marker genes (E), and the visceral fat marker Wt1 (F) in dermal, inguinal, and gonadal adipocytes (n = 5–10). ND, not detected. (G) Liquid chromatography–tandem mass spectrometry analysis of indicated metabolites extracted from dermal, inguinal, and gonadal adipocytes (n = 4 samples; each sample contained adipocytes from 3–4 mice). (H) Expression profile of Camp in different adipocytes, fat pads, and tissues in 2-month-old mice (n = 2). (I) Camp gene expression in 30-day-old mice (n = 6–7, each sample pooled from 3–4 mice). All results were confirmed in at least 2 independent experiments. Data are shown as mean ± SD. P values were calculated with 2-tailed Student’s t test (I) or 2-way ANOVA with Tukey’s test (D, E, and G). A P value less than 0.05 is considered significant. *P < 0.05, **P < 0.01.