Prospective isolation of human erythroid lineage-committed progenitors

Author:

Mori Yasuo,Chen James Y.,Pluvinage John V.,Seita Jun,Weissman Irving L.

Abstract

Determining the developmental pathway leading to erythrocytes and being able to isolate their progenitors are crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Here we show that the human erythrocyte progenitor (hEP) can be prospectively isolated from adult bone marrow. We found three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage CD34+ CD38+ IL-3Rα CD45RA) population. Both CD71 CD105 and CD71+ CD105 MEPs, at least in vitro, still retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter subpopulation is skewed in differentiation toward the erythroid lineage. Notably, the proliferative and differentiation output of the CD71intermediate(int)/+ CD105+ subset of cells within the MEP population was completely restricted to the erythroid lineage with the loss of MegK potential. CD71+ CD105 MEPs are erythrocyte-biased MEPs (E-MEPs) and CD71int/+ CD105+ cells are EPs. These previously unclassified populations may facilitate further understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Heart, Lung, and Blood Institute

California Institute of Regenerative Medicine

Leukemia and Lymphoma Society

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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