You Wenjing, Xu Ziye, Chen Wentao, Yang Xin, Liu Shiqi, Wang Liyi, Tu Yuang, Zhou Yanbing, Valencak Teresa G, Wang Yizhen, Kuang Shihuan, Shan Tizhong
College of Animal Sciences, Zhejiang University, Hangzhou, China.
The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China.
Research (Wash D C). 2023 Nov 8;6:0268. doi: 10.34133/research.0268. eCollection 2023.
Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis and crucial for systemic metabolism. Under chronic cold exposures and high-fat diet challenges, BAT undergoes robust remodeling to adapt to physiological demands. However, whether and how BAT regenerates after acute injuries are poorly understood. Here, we established a novel BAT injury and regeneration model (BAT-IR) in mice and performed single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to determine cellular and transcriptomic dynamics during BAT-IR. We further defined distinct fibro-adipogenic and myeloid progenitor populations contributing to BAT regeneration. Cell trajectory and gene expression analyses uncovered the involvement of MAPK, Wnt, and Hedgehog (Hh) signaling pathways in BAT regeneration. We confirmed the role of Hh signaling in BAT development through mediated conditional knockout (cKO) of the gene to activate Hh signaling in BAT and muscle progenitors. Our BAT-IR model therefore provides a paradigm to identify conserved cellular and molecular mechanisms underlying BAT development and remodeling.
棕色脂肪组织（BAT）是非颤抖性产热的主要部位，对全身代谢至关重要。在长期寒冷暴露和高脂饮食挑战下，BAT会经历强大的重塑过程以适应生理需求。然而，急性损伤后BAT是否以及如何再生，目前尚不清楚。在此，我们在小鼠中建立了一种新型的BAT损伤和再生模型（BAT-IR），并进行了单细胞RNA测序（scRNA-seq）和批量RNA测序，以确定BAT-IR过程中的细胞和转录组动态变化。我们进一步定义了对BAT再生有贡献的不同的成纤维脂肪生成和髓系祖细胞群体。细胞轨迹和基因表达分析揭示了丝裂原活化蛋白激酶（MAPK）、Wnt和刺猬（Hh）信号通路参与BAT再生。我们通过介导基因的条件性敲除（cKO）以激活BAT和肌肉祖细胞中的Hh信号，证实了Hh信号在BAT发育中的作用。因此，我们的BAT-IR模型为识别BAT发育和重塑背后保守的细胞和分子机制提供了一个范例。
