Cellular and Transcriptional Dynamics during Brown Adipose Tissue Regeneration under Acute Injury

Wenjing You; Ziye Xu; Wentao Chen; Xin Yang; Shiqi Liu; Liyi Wang; Yuang Tu; Yanbing Zhou; Teresa G Valencak; Yizhen Wang; Shihuan Kuang; Tizhong Shan

doi:10.34133/research.0268

Cellular and Transcriptional Dynamics during Brown Adipose Tissue Regeneration under Acute Injury

Research (Wash D C). 2023 Nov 8:6:0268. doi: 10.34133/research.0268. eCollection 2023.

Authors

Wenjing You^{1

2

3}, Ziye Xu^{1

4}, Wentao Chen^{1

2

3}, Xin Yang⁵, Shiqi Liu^{1

2

3}, Liyi Wang^{1

2

3}, Yuang Tu^{1

2

3}, Yanbing Zhou^{1

2

3}, Teresa G Valencak¹, Yizhen Wang^{1

2

3}, Shihuan Kuang⁵, Tizhong Shan^{1

2

3}

Affiliations

¹ College of Animal Sciences, Zhejiang University, Hangzhou, China.
² The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China.
³ Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Hangzhou, China.
⁴ Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁵ Department of Animal Sciences, Purdue University, West Lafayette, IN, USA.

Abstract

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 Myf5^Cre-mediated conditional knockout (cKO) of the Sufu 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.