Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures

  1. Shannon Rausser
  2. Caroline Trumpff
  3. Marlon A McGill
  4. Alex Junker
  5. Wei Wang
  6. Siu-hong Ho
  7. Anika Mitchell
  8. Kalpita R Karan
  9. Catherine E Monk
  10. Suzanne C Segerstrom
  11. Rebecca G Reed
  12. Martin Picard  Is a corresponding author
  1. Columbia University Irving Medical Center, United States
  2. University of Kentucky, United States
  3. University of Pittsburgh, United States

Abstract

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly-defined immune cell subtypes, we quantify the natural variation in citrate synthase, mitochondrial DNA copy number (mtDNAcn), and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning 4 decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, which are masked or blunted in mixed PBMCs. Finally, a proof-of-concept, repeated-measures study in a single individual validates cell type differences and also reveals week-to-week changes in mitochondrial activities. Larger studies are required to validate and mechanistically extend these findings. These mitochondrial phenotyping data build upon established immunometabolic differences among leukocyte sub-populations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health.

Data availability

All data generated and analyzed during this study, including mitochondrial biochemistry, mtDNA content, and blood chemistry, cell counts from CBC and flow cytometry, and de-identified participant information are included in the supporting data files. Source data files have been provided for Figures 1-9, and for figure supplements (Figure 1-figure supplement 3, Figure 2-figure supplement 1, Figure 4-figure supplement 1, Figure 4-figure supplement 2, Figure 6-figure supplement 1, Figure 6-figure supplement 2, Figure 6-figure supplement 3, and Supplementary file 3). Requests for resources or other information should be directed to and will be fulfilled by the corresponding author.

Article and author information

Author details

  1. Shannon Rausser

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0425-1571
  2. Caroline Trumpff

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Marlon A McGill

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alex Junker

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Wei Wang

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9890-2122
  6. Siu-hong Ho

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Anika Mitchell

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kalpita R Karan

    Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Catherine E Monk

    Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Suzanne C Segerstrom

    University of Kentucky, Lexington, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Rebecca G Reed

    University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Martin Picard

    Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, United States
    For correspondence
    martin.picard@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2835-0478

Funding

Nathaniel Wharton Fund

  • Martin Picard

National Institutes of Health (MH119336,GM119793,MH122706,AG066828,AG056635,AG026307,UL1TR001873)

  • Martin Picard

National Institutes of Health (P30CA013696)

  • Wei Wang

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

Reviewing Editor

  1. Simon C Johnson, University of Washington, United States

Ethics

Human subjects: The study was approved by New York State Psychiatric Institute (Protocol #7618) and all participants provided written informed consent for the study procedures and reporting of results.

Version history

  1. Preprint posted: October 16, 2020 (view preprint)
  2. Received: June 2, 2021
  3. Accepted: October 26, 2021
  4. Accepted Manuscript published: October 26, 2021 (version 1)
  5. Version of Record published: November 24, 2021 (version 2)

Copyright

© 2021, Rausser 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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  1. Shannon Rausser
  2. Caroline Trumpff
  3. Marlon A McGill
  4. Alex Junker
  5. Wei Wang
  6. Siu-hong Ho
  7. Anika Mitchell
  8. Kalpita R Karan
  9. Catherine E Monk
  10. Suzanne C Segerstrom
  11. Rebecca G Reed
  12. Martin Picard
(2021)
Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
eLife 10:e70899.
https://doi.org/10.7554/eLife.70899

Share this article

https://doi.org/10.7554/eLife.70899

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