HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity

  1. Tamar Tak
  2. Giulio Prevedello
  3. Gaël Simon
  4. Noémie Paillon
  5. Camélia Benlabiod
  6. Caroline Marty
  7. Isabelle Plo
  8. Ken R Duffy
  9. Leïla Perié  Is a corresponding author
  1. Institut Curie, France
  2. INSERM, Gustave Roussy, France
  3. Institut Gustave Roussy; INSERM U1170, France
  4. Maynooth University, Ireland

Abstract

High-throughput single cell methods have uncovered substantial heterogeneity in the pool of hematopoietic stem and progenitor cells (HSPCs), but how much instruction is inherited by offspring from their heterogeneous ancestors remains unanswered. Using a method that enables simultaneous determination of common ancestor, division number, and differentiation status of a large collection of single cells, our data revealed that murine cells that derived from a common ancestor had significant similarities in their division progression and differentiation outcomes. Although each family diversifies, the overall collection of cell types observed is composed of homogeneous families. Heterogeneity between families could be explained, in part, by differences in ancestral expression of cell-surface markers. Our analyses demonstrate that fate decision by cells are largely inherited from ancestor cells, indicating the importance of common ancestor effects. These results may have ramifications for bone marrow transplantation and leukemia, where substantial heterogeneity in HSPC behavior is observed.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data has been provided for Figures 1-4 in supplemental File 1.

Article and author information

Author details

  1. Tamar Tak

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5959-7927
  2. Giulio Prevedello

    CNRS UMR 3348, Institut Curie, Orsay, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9857-2351
  3. Gaël Simon

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Noémie Paillon

    UMR168 Physico-chimie, Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6848-3016
  5. Camélia Benlabiod

    UMR1287, INSERM, Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Caroline Marty

    UMR1287, INSERM, Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Isabelle Plo

    INSERM U1170, Institut Gustave Roussy; INSERM U1170, VILLEJUIF, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Ken R Duffy

    Hamilton Institute, Maynooth University, Co Kildare, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  9. Leïla Perié

    UMR168 Physico-chimie, Institut Curie, Paris, France
    For correspondence
    leila.perie@curie.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0798-4498

Funding

Bettencourt-Schue (ATIP-Avenir)

  • Leïla Perié

Labex CelTisPhyBio (ANR-10-LBX-0038)

  • Leïla Perié

Idex (Paris-Sciece-Lettres Program ANR-10-IDEX-0001-02 PSL)

  • Leïla Perié

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

Ethics

Animal experimentation: All the experimental procedures were approved by the local ethics committee (Comité d'Ethique en expérimentation animale de l'Institut Curie) under approval number DAP 2016 006.

Copyright

© 2021, Tak 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. Tamar Tak
  2. Giulio Prevedello
  3. Gaël Simon
  4. Noémie Paillon
  5. Camélia Benlabiod
  6. Caroline Marty
  7. Isabelle Plo
  8. Ken R Duffy
  9. Leïla Perié
(2021)
HSPCs display within-family homogeneity in differentiation and proliferation despite population heterogeneity
eLife 10:e60624.
https://doi.org/10.7554/eLife.60624

Share this article

https://doi.org/10.7554/eLife.60624

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