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 6

In vivo detection of proliferation and transformation of dedifferentiated dermal adipocytes.

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In vivo detection of proliferation and transformation of dedifferentiate...
(A) Schematic diagram of experimental design: Preexisting adipocytes were labeled during the second anagen in AdipoChaser-mTmG mice (Dox: P28–P35). The mice were then put on normal chow diet until a prolonged period into the second telogen. One group of mice was on normal chow diet and was injected with BrdU daily (P56–P63). Another group of mice was switched to HFD, and injected with BrdU daily (P56–P63). Skin was collected at P63 for GFP (green), BrdU (red), and DAPI (blue) staining. Colocalization of GFP and BrdU was observed in the HFD group, but not in the chow diet group. n = 3 mice per group. (B) Schematic diagram of experimental design: Preexisting adipocytes were labeled during second anagen in AdipoChaser-mTmG mice (Dox: P28–P35). Then mice were put on normal chow diet until prolonged second telogen. From P56, mice were injected s.c. with vehicle/bleomycin daily for a total of 21 days. Skin was collected at P77 for GFP (green), α-SMA (red), and DAPI (blue) staining. Colocalization of GFP and α-SMA was observed in the bleomycin-treated group, but not in the vehicle group. n = 4 mice per group. Results were confirmed in 3 independent experiments. Scale bars: 50 μm; ×2 magnification for insets.