Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
- Institut Curie, France
- The Netherlands Cancer Institute, Netherlands
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.-
Article and author information
Author details
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.
Reviewing Editor
- Atsushi Iwama, The University of Tokyo, Japan
Ethics
Animal experimentation: All procedures were approved by the responsible national ethics committee (APAFIS#10955-201708171446318 v1).
Version history
- Preprint posted: April 20, 2020 (view preprint)
- Received: January 26, 2021
- Accepted: February 14, 2022
- Accepted Manuscript published: February 15, 2022 (version 1)
- Version of Record published: February 28, 2022 (version 2)
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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Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells
eLife 11:e66922.
https://doi.org/10.7554/eLife.66922
Further reading
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