Identification of unipotent megakaryocyte progenitors in human hematopoiesis

Kohta Miyawaki, Hiromi Iwasaki, Takashi Jiromaru, Hirotake Kusumoto, Ayano Yurino, Takeshi Sugio, Yasufumi Uehara, Jun Odawara, Shinya Daitoku, Yuya Kunisaki, Yasuo Mori, Yojiro Arinobu, Hirofumi Tsuzuki, Yoshikane Kikushige, Tadafumi Iino, Koji Kato, Katsuto Takenaka, Toshihiro Miyamoto, Takahiro Maeda, Koichi Akashi

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20 Citations (Scopus)

Abstract

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. (Blood. 2017;129(25): 3332-3343).

Original languageEnglish
Pages (from-to)3332-3343
Number of pages12
JournalBlood
Volume129
Issue number25
DOIs
Publication statusPublished - Jun 22 2017

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Miyawaki, K., Iwasaki, H., Jiromaru, T., Kusumoto, H., Yurino, A., Sugio, T., ... Akashi, K. (2017). Identification of unipotent megakaryocyte progenitors in human hematopoiesis. Blood, 129(25), 3332-3343. https://doi.org/10.1182/blood-2016-09-741611