Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells.
cellular barcoding
erythropoietin
hematopoietic stem cell
immunology
inflammation
mouse
multipotent progenitor
regenerative medicine
single cell
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
26
01
2021
accepted:
14
02
2022
pubmed:
16
2
2022
medline:
5
4
2022
entrez:
15
2
2022
Statut:
epublish
Résumé
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-biased and myeloid-B-cell-dendritic cell-biased clones. Single-cell RNA sequencing 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.
Identifiants
pubmed: 35166672
doi: 10.7554/eLife.66922
pii: 66922
pmc: PMC8884727
doi:
pii:
Substances chimiques
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Eisele et al.
Déclaration de conflit d'intérêts
AE, JC, AM, ET, ST, CC, FC, TT, AL, JU, LP No competing interests declared
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