1. Cell Biology
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Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes

  1. Prashant Rajbhandari  Is a corresponding author
  2. Douglas Arneson
  3. Sydney K Hart
  4. In Sook Ahn
  5. Graciel Diamante
  6. Luis C Santos
  7. Nima Zaghari
  8. An-Chieh Feng
  9. Brandon J Thomas
  10. Laurent Vergnes
  11. Stephen D Lee
  12. Abha K Rajbhandari
  13. Karen Reue
  14. Stephen T Smale
  15. Xia Yang
  16. Peter Tontonoz  Is a corresponding author
  1. University of California, Los Angeles, United States
  2. Icahn School of Medicine at Mount Sinai, United States
Research Article
  • Cited 34
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Cite this article as: eLife 2019;8:e49501 doi: 10.7554/eLife.49501

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

Article and author information

Author details

  1. 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.
  2. Douglas Arneson

    Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  3. 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.
  4. In Sook Ahn

    Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Graciel Diamante

    Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  6. 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.
  7. Nima Zaghari

    Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  8. 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.
  9. 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.
  10. Laurent Vergnes

    Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  11. Stephen D Lee

    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  12. 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.
  13. Karen Reue

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  14. Stephen T Smale

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  15. Xia Yang

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  16. 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.
    ORCID icon "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.

Reviewing Editor

  1. Michael Czech, University of Massachusetts Medical School, United States

Publication history

  1. Received: June 19, 2019
  2. Accepted: October 22, 2019
  3. Accepted Manuscript published: October 23, 2019 (version 1)
  4. Version of Record published: November 7, 2019 (version 2)

Copyright

© 2019, Rajbhandari et al.

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.

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