Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes

Abstract
Data availability
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Abstract

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor a in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Ra deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

Data availability

Sequencing data have been deposited to GEO.

The following data sets were generated

(2019) Single cell sequencing of stromal vascular fraction (SVF) under B3-adrenergic agonist stimulation and mature adipocytes under cold exposure and B3-adrenergic agonist stimulation
NCBI Gene Expression Omnibus, GSE133486.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133486

Article and author information

Author details

Prashant Rajbhandari

Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
prashant.rajbhandari@gmail.com

Competing interests
No competing interests declared.
Douglas Arneson

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Sydney K Hart

Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, United States

Competing interests
No competing interests declared.
In Sook Ahn

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Graciel Diamante

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Luis C Santos

Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, United States

Competing interests
No competing interests declared.
Nima Zaghari

Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
An-Chieh Feng

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Brandon J Thomas

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Laurent Vergnes

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Stephen D Lee

Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Abha K Rajbhandari

Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States

Competing interests
No competing interests declared.
Karen Reue

Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Stephen T Smale

Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Xia Yang

Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Peter Tontonoz

Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
ptontonoz@mednet.ucla.edu

Competing interests
Peter Tontonoz, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-1259-0477

Funding

National Institutes of Health (K99 DK114571)

Prashant Rajbhandari

National Institutes of Health (DK063491)

Peter Tontonoz

National Institutes of Health (DK120851)

Peter Tontonoz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (99-131) of the University of California, Los Angeles.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.