1. Immunology and Inflammation
  2. Stem Cells and Regenerative Medicine

Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

  1. Almut S Eisele
  2. Jason Cosgrove
  3. Aurelie Magniez
  4. Emilie Tubeuf
  5. Sabrina Tenreira Bento
  6. Cecile Conrad
  7. Fanny Cayrac
  8. Tamar Tak
  9. Anne-Marie Lyne
  10. Jos Urbanus
  11. Leïla Perié  Is a corresponding author
  1. Institut Curie, France
  2. The Netherlands Cancer Institute, Netherlands
https://doi.org/10.7554/eLife.66922
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  1. Almut S Eisele
  2. Jason Cosgrove
  3. Aurelie Magniez
  4. Emilie Tubeuf
  5. Sabrina Tenreira Bento
  6. Cecile Conrad
  7. Fanny Cayrac
  8. Tamar Tak
  9. Anne-Marie Lyne
  10. Jos Urbanus
  11. Leïla Perié
(2022)
Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
eLife 11:e66922.
https://doi.org/10.7554/eLife.66922
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Abstract

The cytokine erythropoietin (EPO) is a potent inducer of erythrocyte development and one of the most prescribed biopharmaceuticals. The action of EPO on erythroid progenitor cells is well established, but its direct action on hematopoietic stem and progenitor cells (HSPCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single murine HSPCs, after ex vivo EPO-exposure and transplantation, in five different hematopoietic cell lineages, and observed the transient occurrence of high-output Myeloid-Erythroid-megaKaryocyte (MEK)-biased and Myeloid-B-cell-Dendritic cell (MBDC)-biased clones. Single-cell RNA sequencing (ScRNAseq) analysis of ex vivo EPO-exposed HSPCs revealed that EPO induced the upregulation of erythroid associated genes in a subset of HSPCs, overlapping with multipotent progenitor (MPP) 1 and MPP2. Transplantation of Barcoded EPO-exposed-MPP2 confirmed their enrichment in Myeloid-Erythroid-biased clones. Collectively, our data show that EPO does act directly on MPP independent of the niche, and modulates fate by remodeling the clonal composition of the MPP pool.

Data availability

all data and scripts are available on the github of the Perie labhttps://github.com/PerieTeam/Eisele-et-al.-

The following data sets were generated

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Author details

  1. Almut S Eisele

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

  2. Jason Cosgrove

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

  3. Aurelie Magniez

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

  4. Emilie Tubeuf

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

  5. Sabrina Tenreira Bento

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

  6. Cecile Conrad

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

  7. Fanny Cayrac

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

  8. Tamar Tak

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

  9. Anne-Marie Lyne

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

  10. Jos Urbanus

    Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  11. Leïla Perié

    CNRS 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

Atip Avenir CNRS

  • Leïla Perié

Labex Celtisphybio (ANR-11-LABX-0038)

  • Leïla Perié

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

  • Leïla Perié

H2020 European Research Council (758170-Microbar)

  • Leïla Perié

H2020 Marie Skłodowska-Curie Actions (666003)

  • Almut S Eisele

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 procedures were approved by the responsible national ethics committee (APAFIS#10955-201708171446318 v1).

Copyright

© 2022, Eisele 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. Almut S Eisele
  2. Jason Cosgrove
  3. Aurelie Magniez
  4. Emilie Tubeuf
  5. Sabrina Tenreira Bento
  6. Cecile Conrad
  7. Fanny Cayrac
  8. Tamar Tak
  9. Anne-Marie Lyne
  10. Jos Urbanus
  11. Leïla Perié
(2022)
Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
eLife 11:e66922.
https://doi.org/10.7554/eLife.66922

Share this article

https://doi.org/10.7554/eLife.66922

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