Distinct routes of lineage development reshape the human blood hierarchy across ontogeny
Top Cited Papers
- 7 January 2016
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 351 (6269), 139-+
- https://doi.org/10.1126/science.aab2116
Abstract
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.Keywords
Funding Information
- Canadian Institute of Health Research (CIHR)
- Aplastic Anemia and Myelodysplasia Association of Canada
- Ontario Institute of Cancer Research (OICR)
- Ontario Ministry of Research and Innovation
- Wellcome Trust
- Canadian Cancer Society
- Terry Fox Foundation
- Ontario Genomics Institute
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