CD41 Marks the Initial Myelo‐Erythroid Lineage Specification in Adult Mouse Hematopoiesis: Redefinition of Murine Common Myeloid Progenitor

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 pr...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2015-03, Vol.33 (3), p.976-987
Main Authors: Miyawaki, Kohta, Arinobu, Yojiro, Iwasaki, Hiromi, Kohno, Kentaro, Tsuzuki, Hirofumi, Iino, Tadafumi, Shima, Takahiro, Kikushige, Yoshikane, Takenaka, Katsuto, Miyamoto, Toshihiro, Akashi, Koichi
Format: Article
Language:English
Subjects:
Animals
Bone marrow
CD41
Cell Differentiation - physiology
Cell Lineage
Cells, Cultured
Common myeloid progenitors
GATA‐1 transcription factor
Gene expression
Gene Expression Profiling
Hematopoiesis - physiology
Hematopoietic stem cells
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Leukemia, Myeloid - pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myeloid leukemia
Myeloid Progenitor Cells - cytology
Myeloid Progenitor Cells - metabolism
Platelet Membrane Glycoprotein IIb - metabolism
Sepsis
Stem cells
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Summary: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 CD41hi 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 CD41hi 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 CD41hi CMP and the LMPP populations. Stem Cells 2015;33:976–987
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1906