期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 31, 页码 9638-9643出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1512076112
关键词
erythroid progenitor; endoglin; lineage commitment; hematopoiesis; transcription factor
资金
- Japan Society for the Promotion of Science
- National Cancer Institute
- National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 CA086065, U01 HL099999]
- California Institute for Regenerative Medicine [RT2-02060]
- Leukemia & Lymphoma Society [700709]
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-3R alpha(-) 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 sub-population is skewed in differentiation toward the erythroid lineage. Notably, the proliferative and differentiation output of the CD71(intermediate(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 erythrocytebiased MEPs (E-MEPs) and CD71(int/+) 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.
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