Identification of two distinct pathways of human myelopoiesis

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Science Immunology  24 May 2019:
Vol. 4, Issue 35, eaau7148
DOI: 10.1126/sciimmunol.aau7148

Goodbye CMPs

Advances in single-cell analyses continue to profoundly change our understanding of hematopoiesis. Here, using single-cell RNA sequencing in conjunction with functional studies, Drissen et al. studied the differentiation potentials of human common myeloid progenitor (CMP) cells. They report that CMPs that have been defined on the basis of cell surface markers are a mixture of at least two cell types with the potential to give rise to either mast cells/basophils/eosinophils or neutrophils/monocytes. In other words, they report that CMPs having the potential to give rise to all myeloid cell types do not exist. Furthermore, they found that the cells in the former group retain the potential to give rise to megakaryocytes and erythrocytes, whereas cells in the latter groups retain lymphoid potential.


Human myelopoiesis has been proposed to occur through oligopotent common myeloid progenitor (CMP) and lymphoid-primed multipotent progenitor (LMPP) populations. However, other studies have proposed direct commitment of multipotent cells to unilineage fates, without specific intermediary lineage cosegregation patterns. We here show that distinct human myeloid progenitor populations generate the neutrophil/monocyte and mast cell/basophil/eosinophil lineages as previously shown in mouse. Moreover, we find that neutrophil/monocyte potential selectively cosegregates with lymphoid lineage and mast cell/basophil/eosinophil potentials with megakaryocyte/erythroid potential early during lineage commitment. Furthermore, after this initial commitment step, mast cell/basophil/eosinophil and megakaryocyte/erythroid potentials colocalize at the single-cell level in restricted oligopotent progenitors. These results show that human myeloid lineages are generated through two distinct cellular pathways defined by complementary oligopotent cell populations.

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