Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice

Stem Cell Reports
Rashim Pal SinghBen Wielockx

Abstract

The hematopoietic stem cell (HSC) compartment consists of a small pool of cells capable of replenishing all blood cells. Although it is established that the hematopoietic system is assembled as a hierarchical organization under steady-state conditions, emerging evidence suggests that distinct differentiation pathways may exist in response to acute stress. However, it remains unclear how different hematopoietic stem and progenitor cell subpopulations behave under sustained chronic stress. Here, by using adult transgenic mice overexpressing erythropoietin (EPO; Tg6) and a combination of in vivo, in vitro, and deep-sequencing approaches, we found that HSCs respond differentially to chronic erythroid stress compared with their closely related multipotent progenitors (MPPs). Specifically, HSCs exhibit a vastly committed erythroid progenitor profile with enhanced cell division, while MPPs display erythroid and myeloid cell signatures and an accumulation of uncommitted cells. Thus, our results identify HSCs as master regulators of chronic stress erythropoiesis, potentially circumventing the hierarchical differentiation-detour.

Citations

Jul 25, 2018·International Journal of Molecular Sciences·Geoffrey BrownPanagiotis Tsapogas
Dec 22, 2019·International Journal of Molecular Sciences·Geoffrey BrownIsidro Sánchez-García
Mar 12, 2020·Cells·Robert F PaulsonYuanting Chen
Apr 8, 2020·Frontiers in Cell and Developmental Biology·Kateřina FaltusováEmanuel Nečas
Jul 6, 2019·Frontiers in Cell and Developmental Biology·Geoffrey Brown, Rhodri Ceredig
Jun 3, 2021·Bioengineering·Geoffrey Brown
Feb 24, 2021·Blood·Sundary SormendiBen Wielockx
Oct 1, 2021·Leukemia·Vinothkumar RajanJason N Berman

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Methods Mentioned

BETA
transgenic
fluorescence-activated cell sorting
RNA-seq
FACS

Software Mentioned

GSEA
featureCounts
CLUEGO
DESeq2
BWA
clusterProfiler R package
FastQC
DEseq2 R package
Cytoscape
GraphPad Prism

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