Work

Transcriptomic plasticity of cholinergic adipose macrophages in the acute thermogenic response

Year: 2025

Type: article

Abstract: Cholinergic adipose macrophages (ChAMs) have recently been shown to regulate the acute thermogenic response in subcutaneous white adipose tissue, yet their transcriptomic dynamics are poorly understood, and little is known about their origins or identity. Using single-cell RNA sequencing (scRNAseq), we profiled ChAT-eGFP+ cells (expressing choline acetyltransferase) from subcutaneous white adipose tissue of mice housed at thermoneutrality or after acute cold exposure. We identified twelve distinct clusters of ChAT-expressing cells, predominated by hematopoietic cell types. Specifically, ChAMs exhibited increased proportions and Chat expression after acute cold. Widespread differential gene expression was induced in ChAMs after cold compared to thermoneutrality, with cold-enriched pathways in immune signaling, chemotaxis, and metabolism. Several ChAM subsets were uncovered that resembled previously reported adipose macrophage subpopulations. ChAMs were predicted to have mixed origins, derived from adult bone marrow and embryonically. These findings provide a high granularity assessment of cholinergic immune cells in fat, and we highlight the transcriptomic plasticity and mixed origins of ChAMs, suggesting their therapeutic potential for metabolic diseases.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110925

Authors: Alexander J. Knights, Evan J. Kim, Shanshan Liu, Jun Wu

Institutions: Washington University in St. Louis, University of Michigan

Language: English

Topic: Adipose Tissue and Metabolism

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430