Identification of unipotent megakaryocyte progenitors in human hematopoiesis.
The developmental pathway for human megakaryocytes remains unclear, and the definition of pure unipotent megakaryocyte progenitor is still controversial. Using single-cell transcriptome analysis, we have identified a cluster of cells within immature hematopoietic stem- and progenitor-cell populations that specifically expresses genes related to the megakaryocyte lineage. We used CD41 as a positive marker to identify these cells within the CD34+CD38+IL-3RαdimCD45RA-common myeloid progenitor (CMP) population. These cells lacked erythroid and granulocyte-macrophage potential but exhibited robust differentiation into the megakaryocyte lineage at a high frequency, both in vivo and in vitro. The efficiency and expansion potential of these cells exceeded those of conventional bipotent megakaryocyte/erythrocyte progenitors. Accordingly, the CD41+CMP was defined as a unipotent megakaryocyte progenitor (MegP) that is likely to represent the major pathway for human megakaryopoiesis, independent of canonical megakaryocyte-erythroid lineage bifurcation. In the bone marrow of patients with essential thrombocythemia, the MegP population was significantly expanded in the context of a high burden of Janus kinase 2 mutations. Thus, the prospectively isolatable and functionally homogeneous human MegP will be useful for the elucidation of the mechanisms underlying normal and malignant human hematopoiesis.
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Kohta
K
Miyawaki
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Hiromi
H
Iwasaki
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Takashi
T
Jiromaru
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Hirotake
H
Kusumoto
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Ayano
A
Yurino
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Takeshi
T
Sugio
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Yasufumi
Y
Uehara
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Jun
J
Odawara
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Shinya
S
Daitoku
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Yuya
Y
Kunisaki
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Yasuo
Y
Mori
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Yojiro
Y
Arinobu
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Hirofumi
H
Tsuzuki
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Yoshikane
Y
Kikushige
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Tadafumi
T
Iino
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Koji
K
Kato
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Katsuto
K
Takenaka
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.
Toshihiro
T
Miyamoto
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Takahiro
T
Maeda
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and.|Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Koichi
K
Akashi
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D019070:Cell Lineage; D002478:Cells, Cultured; D006410:Hematopoiesis; D006801:Humans; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000473:pathology; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D059467:Transcriptome
D015703:Antigens, CD; D040201:Platelet Membrane Glycoprotein IIb