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Stem Cells. 2015 Mar;33(3):976-87. doi: 10.1002/stem.1906.

CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor.

Author information

1
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Abstract

Previous studies have predicted that reciprocal activation of GATA-1 and PU.1 regulates myelo-erythroid versus myelo-lymphoid lineage commitment in early hematopoiesis. Such PU.1-activating myelo-lymphoid progenitors exist within the lymphoid-primed multipotent progenitor (LMPP) population at the primitive Lineage(-) Sca-1(+) c-Kit(+) (LSK) stage. We here show that the counterpart of GATA-1-activating myelo-erythroid progenitor resides also at the LSK stage, expressing CD41 at a high level. Purified CD41(hi) LSK cells showed exceedingly strong and prolonged myelo-erythroid-restricted reconstitution, and primed myelo-erythroid gene expression with a more primitive molecular signature as compared to the original common myeloid progenitor (CMP). The CD41(hi) LSK cells more strongly contributed to emergent and malignant myelopoiesis than LMPPs, and produced the original CMP by downregulating Sca-1 and CD41, suggesting that they are the earliest CMPs. Thus, the hematopoietic developmental map should be revised by integrating the primary branchpoint comprised of the new, isolatable CD41(hi) CMP and the LMPP populations.

KEYWORDS:

CD41; Common myeloid progenitors; GATA-1 transcription factor; Hematopoietic stem cells; Myeloid leukemia; Sepsis

PMID:
25446279
DOI:
10.1002/stem.1906
[Indexed for MEDLINE]
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