CUED Publications database

Distinct routes of lineage development reshape the human blood hierarchy across ontogeny.

Notta, F and Zandi, S and Takayama, N and Dobson, S and Gan, OI and Wilson, G and Kaufmann, KB and McLeod, J and Laurenti, E and Dunant, CF and McPherson, JD and Stein, LD and Dror, Y and Dick, JE (2016) Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science, 351. aab2116-aab2116.

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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 resolve myeloid (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.

Item Type: Article
Uncontrolled Keywords: StemCellInstitute Adult Antigens, CD34 Cell Lineage Cell Separation Cells, Cultured Erythroid Cells Fetal Blood Gene Expression Profiling Hematopoiesis Humans Liver Megakaryocyte Progenitor Cells Megakaryocytes Multipotent Stem Cells Myeloid Cells Transcription, Genetic
Divisions: Div D > Structures
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 18:57
Last Modified: 19 Jun 2018 02:19