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The Branching Point in Erythro-Myeloid Differentiation

Development of mature blood cell progenies from hematopoietic stem cells involves the transition through lineage-restricted progenitors. The first branching point along this developmental process is thought to separate the erythro-myeloid and lymphoid lineage fate by yielding two intermediate progen...

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Bibliographic Details
Published in:Cell 2015-12, Vol.163 (7), p.1655-1662
Main Authors: Perié, Leïla, Duffy, Ken R., Kok, Lianne, de Boer, Rob J., Schumacher, Ton N.
Format: Article
Language:English
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Summary:Development of mature blood cell progenies from hematopoietic stem cells involves the transition through lineage-restricted progenitors. The first branching point along this developmental process is thought to separate the erythro-myeloid and lymphoid lineage fate by yielding two intermediate progenitors, the common myeloid and the common lymphoid progenitors (CMPs and CLPs). Here, we use single-cell lineage tracing to demonstrate that so-called CMPs are highly heterogeneous with respect to cellular output, with most individual CMPs yielding either only erythrocytes or only myeloid cells after transplantation. Furthermore, based on the labeling of earlier progenitors, we show that the divergence between the myeloid and erythroid lineage develops within multipotent progenitors (MPP). These data provide evidence for a model of hematopoietic branching in which multiple distinct lineage commitments occur in parallel within the MPP pool. [Display omitted] •Classically defined common myeloid progenitors (CMPs) are highly heterogeneous•Most individual CMPs yield either erythrocytes or myeloid cells•A true common progenitor exists within the multipotent progenitor (MPPs) pool•The divergence between myeloid cells and erythrocytes starts within the MPPs The so-called common myeloid progenitors (CMPs) are highly heterogeneous, with most individual CMPs yielding either only erythrocytes or only myeloid cells after transplantation. This provides in vivo evidence for a model of early parallel lineage branching within the multipotent progenitor pool that is in sharp contrast with the standard model of hematopoiesis.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2015.11.059