Identification of unipotent megakaryocyte progenitors in human hematopoiesis.
Blood
; 129(25): 3332-3343, 2017 06 22.
Article
em En
| MEDLINE
| ID: mdl-28336526
ABSTRACT
The developmental pathway for human megakaryocytes remains unclear, and the definition of pure unipotent megakaryocyte progenitor is still controversial. Using single-cell transcriptome analysis, we have identified a cluster of cells within immature hematopoietic stem- and progenitor-cell populations that specifically expresses genes related to the megakaryocyte lineage. We used CD41 as a positive marker to identify these cells within the CD34+CD38+IL-3RαdimCD45RA- common myeloid progenitor (CMP) population. These cells lacked erythroid and granulocyte-macrophage potential but exhibited robust differentiation into the megakaryocyte lineage at a high frequency, both in vivo and in vitro. The efficiency and expansion potential of these cells exceeded those of conventional bipotent megakaryocyte/erythrocyte progenitors. Accordingly, the CD41+ CMP was defined as a unipotent megakaryocyte progenitor (MegP) that is likely to represent the major pathway for human megakaryopoiesis, independent of canonical megakaryocyte-erythroid lineage bifurcation. In the bone marrow of patients with essential thrombocythemia, the MegP population was significantly expanded in the context of a high burden of Janus kinase 2 mutations. Thus, the prospectively isolatable and functionally homogeneous human MegP will be useful for the elucidation of the mechanisms underlying normal and malignant human hematopoiesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Megacariócitos
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Células Progenitoras de Megacariócitos
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Hematopoese
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
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Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article