Apr 20, 2020

Erythropoietin directly affects single hematopoietic stem cell differentiation after transplantation

BioRxiv : the Preprint Server for Biology
A. S. EiseleLeila Perie

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 action on hematopoietic stem cells (HSCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single HSCs, after in vitro EPO exposure and transplantation, in five different hematopoietic cell lineages, and observed the occurrence of high-output Myeloid-Erythroid-megaKaryocyte (MEK)-biased and Myeloid-B-cell-Dendritic cell (MBDC)-biased clones. ScRNAseq analysis of in vitro EPO-exposed HSCs revealed upregulation of erythroid associated genes in a subset of HSCs. Collectively, as well as demonstrating a direct effect of EPO on HSCs, our results suggest an EPO-mediated induction of MEK-bias in multi-outcome HSCs, and that this change in output is functionally compensated by MBDC-biased HSCs.

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Mentioned in this Paper

Transcriptional Regulation
Three-dimensional
Diffusion Weighted Imaging
Transcription, Genetic
SPT6 Protein
Cell Nucleus
Protein-Protein Interaction
Site
Binding (Molecular Function)
Structure

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