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

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.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine

“…Drawing upon insights gleaned from existing literature, the hallmarks of regeneration can be conveniently categorized into three principal domains: the classification of regeneration types, the underlying mechanisms governing regeneration, and the regulatory processes that orchestrate these events. Regeneration is typically classified into three types, complete, incomplete, or compensatory, depending on the extent of restoration achieved [ 214 – 217 ]. Complete regeneration entails the comprehensive reinstatement of a lost or damaged component, achieving both structural and functional recovery.…”