title: CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor.
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.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Miyawaki
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Arinobu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kohno
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tsuzuki
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Iino
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shima
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Kikushige
authors.forename: Katsuto
authors.initials: K
authors.lastname: Takenaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism*
chemical_list: D040201:Platelet Membrane Glycoprotein IIb
keywords: CD41; Common myeloid progenitors; GATA-1 transcription factor; Hematopoietic stem cells; Myeloid leukemia; Sepsis