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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-09-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114002392 |
| _version_ | 1811259245319946240 |
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| author | Stanislav Rybtsov Antoniana Batsivari Kateryna Bilotkach Daria Paruzina Jordi Senserrich Oleg Nerushev Alexander Medvinsky |
| author_facet | Stanislav Rybtsov Antoniana Batsivari Kateryna Bilotkach Daria Paruzina Jordi Senserrich Oleg Nerushev Alexander Medvinsky |
| author_sort | Stanislav Rybtsov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T18:27:33Z |
| format | Article |
| id | doaj.art-cbe06e1d40b042bc9290a69543d0d1dd |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-12T18:27:33Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-cbe06e1d40b042bc9290a69543d0d1dd2022-12-22T03:21:12ZengElsevierStem Cell Reports2213-67112014-09-013348950110.1016/j.stemcr.2014.07.009Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43− Embryonic PrecursorStanislav Rybtsov0Antoniana Batsivari1Kateryna Bilotkach2Daria Paruzina3Jordi Senserrich4Oleg Nerushev5Alexander Medvinsky6MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKSchool of Chemistry, EaStCHEM, The University of Edinburgh, Edinburgh EH9 3JJ, Scotland, UKMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, Scotland, UKDefinitive 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.http://www.sciencedirect.com/science/article/pii/S2213671114002392 |
| spellingShingle | Stanislav Rybtsov Antoniana Batsivari Kateryna Bilotkach Daria Paruzina Jordi Senserrich Oleg Nerushev Alexander Medvinsky Tracing the Origin of the HSC Hierarchy Reveals an SCF-Dependent, IL-3-Independent CD43− Embryonic Precursor Stem Cell Reports |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114002392 |
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