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Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor
Definitive hematopoietic stem cells (HSCs) develop in the aorta gonad mesonephros (AGM) region in a stepwise manner. Type I pre-HSCs express CD41 but lack CD45 expression, which is subsequently upregulated in type II pre-HSCs prior to their maturation into definitive HSCs. Here, using ex vivo modeli...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266012/ https://www.ncbi.nlm.nih.gov/pubmed/25241746 http://dx.doi.org/10.1016/j.stemcr.2014.07.009 |
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author | Rybtsov, Stanislav Batsivari, Antoniana Bilotkach, Kateryna Paruzina, Daria Senserrich, Jordi Nerushev, Oleg Medvinsky, Alexander |
author_facet | Rybtsov, Stanislav Batsivari, Antoniana Bilotkach, Kateryna Paruzina, Daria Senserrich, Jordi Nerushev, Oleg Medvinsky, Alexander |
author_sort | Rybtsov, Stanislav |
collection | PubMed |
description | Definitive hematopoietic stem cells (HSCs) develop in the aorta gonad mesonephros (AGM) region in a stepwise manner. Type I pre-HSCs express CD41 but lack CD45 expression, which is subsequently upregulated in type II pre-HSCs prior to their maturation into definitive HSCs. Here, using ex vivo modeling of HSC development, we identify precursors of definitive HSCs in the trunk of the embryonic day 9.5 (E9.5) mouse embryo. These precursors, termed here pro-HSCs, are less mature than type I and II pre-HSCs. Although pro-HSCs are CD41(+), they lack the CD43 marker, which is gradually upregulated in the developing HSC lineage. We show that stem cell factor (SCF), but not interleukin-3 (IL-3), is a major effector of HSC maturation during E9–E10. This study extends further the previously established hierarchical organization of the developing HSC lineage and presents it as a differentially regulated four-step process and identifies additional targets that could facilitate the generation of transplantable HSCs from pluripotent cells for clinical needs. |
format | Online Article Text |
id | pubmed-4266012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42660122014-12-16 Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor Rybtsov, Stanislav Batsivari, Antoniana Bilotkach, Kateryna Paruzina, Daria Senserrich, Jordi Nerushev, Oleg Medvinsky, Alexander Stem Cell Reports Article Definitive hematopoietic stem cells (HSCs) develop in the aorta gonad mesonephros (AGM) region in a stepwise manner. Type I pre-HSCs express CD41 but lack CD45 expression, which is subsequently upregulated in type II pre-HSCs prior to their maturation into definitive HSCs. Here, using ex vivo modeling of HSC development, we identify precursors of definitive HSCs in the trunk of the embryonic day 9.5 (E9.5) mouse embryo. These precursors, termed here pro-HSCs, are less mature than type I and II pre-HSCs. Although pro-HSCs are CD41(+), they lack the CD43 marker, which is gradually upregulated in the developing HSC lineage. We show that stem cell factor (SCF), but not interleukin-3 (IL-3), is a major effector of HSC maturation during E9–E10. This study extends further the previously established hierarchical organization of the developing HSC lineage and presents it as a differentially regulated four-step process and identifies additional targets that could facilitate the generation of transplantable HSCs from pluripotent cells for clinical needs. Elsevier 2014-08-28 /pmc/articles/PMC4266012/ /pubmed/25241746 http://dx.doi.org/10.1016/j.stemcr.2014.07.009 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Article Rybtsov, Stanislav Batsivari, Antoniana Bilotkach, Kateryna Paruzina, Daria Senserrich, Jordi Nerushev, Oleg Medvinsky, Alexander Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title | Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title_full | Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title_fullStr | Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title_full_unstemmed | Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title_short | Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43(−) Embryonic Precursor |
title_sort | tracing the origin of the hsc hierarchy reveals an scf-dependent, il-3-independent cd43(−) embryonic precursor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266012/ https://www.ncbi.nlm.nih.gov/pubmed/25241746 http://dx.doi.org/10.1016/j.stemcr.2014.07.009 |
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