Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development
| Autor: | Henninger, Jonathan, Santoso, Buyung, Hans, Stefan, Durand, Ellen, Moore, Jessica, Mosimann, Christian, Brand, Michael, Traver, David, Zon, Leonard |
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| Rok vydání: | 2017 |
| Předmět: |
Platelet Membrane Glycoprotein IIb
Aging Embryonic Development Bone Marrow Cells Cell Count Regenerative Medicine Medical and Health Sciences Erythroid Cells Animals Cell Lineage Transgenes Zebrafish Bone Marrow Transplantation Nonmammalian Staining and Labeling Lasers Biological Sciences Hematopoietic Stem Cells Stem Cell Research Clone Cells Hematopoiesis Embryo Blood Vessels Stem Cell Research - Nonembryonic - Non-Human Granulocytes Developmental Biology |
| Zdroj: | Nature cell biology, vol 19, iss 1 |
| Popis: | Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creERT2 in developing cd41:eGFP+ HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creERT2 that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny. Our findings reveal that approximately 21 HSC clones exist prior to HSC emergence and 30 clones are present during peak production from aortic endothelium. Our methods further reveal that stress haematopoiesis, including sublethal irradiation and transplantation, reduces clonal diversity. Our findings provide quantitative insights into the early clonal events that regulate haematopoietic development. |
| Databáze: | OpenAIRE |
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