期刊
SCIENCE
卷 351, 期 6269, 页码 139-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aab2116
关键词
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资金
- Canadian Institute of Health Research (CIHR)
- Aplastic Anemia and Myelodysplasia Association of Canada
- Ontario Institute of Cancer Research (OICR) through Ontario Ministry of Research and Innovation
- Wellcome Trust Sir Henry Dale Fellowship
- Wellcome Trust
- Medical Research Council
- CIHR
- Canadian Cancer Society
- Terry Fox Foundation
- Genome Canada through the Ontario Genomics Institute
- OICR
- province of Ontario
- Canada Research Chair
- Ontario Ministry of Health and Long-Term Care (OMOHLTC)
In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolvemyeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult two-tier hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.
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