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

## TL;DR

The study explores how brown fat tissue regenerates after injury and identifies key signaling pathways involved in the process.

## Contribution

A novel BAT injury and regeneration model is developed, revealing new cellular and molecular mechanisms in BAT regeneration.

## Key findings

- Distinct fibro-adipogenic and myeloid progenitor populations contribute to BAT regeneration.
- MAPK, Wnt, and Hedgehog signaling pathways are involved in BAT regeneration.
- Activation of Hedgehog signaling in progenitor cells confirms its role in BAT development.

## 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 Myf5Cre-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.