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Hematopoietic stem cells but not multipotent progenitors drive erythropoiesis during chronic erythroid stress in EPO transgenic mice


Singh, Rashim Pal; Grinenko, Tatyana; Ramasz, Beáta; Franke, Kristin; Lesche, Mathias; Dahl, Andreas; Gassmann, Max; Chavakis, Triantafyllos; Henry, Ian; Wielockx, Ben (2018). Hematopoietic stem cells but not multipotent progenitors drive erythropoiesis during chronic erythroid stress in EPO transgenic mice. Stem Cell Reports, 10(6):1908-1919.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:EPO-R, bone marrow, erythropoietin, fate decision, hematopoietic stem cell, hypoxia, progenitors, transgenic
Language:English
Date:5 June 2018
Deposited On:23 Jul 2018 16:59
Last Modified:01 Aug 2018 01:03
Publisher:Cell Press (Elsevier)
ISSN:2213-6711
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.stemcr.2018.04.012
PubMed ID:29754961

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