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

研究成果: ジャーナルへの寄稿記事

16 引用 (Scopus)

抄録

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).

元の言語英語
ページ(範囲)3332-3343
ページ数12
ジャーナルBlood
129
発行部数25
DOI
出版物ステータス出版済み - 6 22 2017

Fingerprint

Megakaryocyte Progenitor Cells
Megakaryocytes
Hematopoiesis
Cells
Janus Kinase 2
Myeloid Progenitor Cells
Macrophages
Hematopoietic Stem Cells
Megakaryocyte-Erythroid Progenitor Cells
Bone
Blood
Genes
Single-Cell Analysis
Population
Essential Thrombocythemia
Erythroid Cells
Gene Expression Profiling
Granulocytes
Bone Marrow
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

これを引用

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

Identification of unipotent megakaryocyte progenitors in human hematopoiesis. / Miyawaki, Kohta; Iwasaki, Hiromi; Jiromaru, Takashi; Kusumoto, Hirotake; Yurino, Ayano; Sugio, Takeshi; Uehara, Yasufumi; Odawara, Jun; Daitoku, Shinya; Kunisaki, Yuya; Mori, Yasuo; Arinobu, Yojiro; Tsuzuki, Hirofumi; Kikushige, Yoshikane; Iino, Tadafumi; Kato, Koji; Takenaka, Katsuto; Miyamoto, Toshihiro; Maeda, Takahiro; Akashi, Koichi.

:: Blood, 巻 129, 番号 25, 22.06.2017, p. 3332-3343.

研究成果: ジャーナルへの寄稿記事

Miyawaki, K, Iwasaki, H, Jiromaru, T, Kusumoto, H, Yurino, A, Sugio, T, Uehara, Y, Odawara, J, Daitoku, S, Kunisaki, Y, Mori, Y, Arinobu, Y, Tsuzuki, H, Kikushige, Y, Iino, T, Kato, K, Takenaka, K, Miyamoto, T, Maeda, T & Akashi, K 2017, 'Identification of unipotent megakaryocyte progenitors in human hematopoiesis', Blood, 巻. 129, 番号 25, pp. 3332-3343. https://doi.org/10.1182/blood-2016-09-741611
Miyawaki K, Iwasaki H, Jiromaru T, Kusumoto H, Yurino A, Sugio T その他. Identification of unipotent megakaryocyte progenitors in human hematopoiesis. Blood. 2017 6 22;129(25):3332-3343. https://doi.org/10.1182/blood-2016-09-741611
Miyawaki, Kohta ; Iwasaki, Hiromi ; Jiromaru, Takashi ; Kusumoto, Hirotake ; Yurino, Ayano ; Sugio, Takeshi ; Uehara, Yasufumi ; Odawara, Jun ; Daitoku, Shinya ; Kunisaki, Yuya ; Mori, Yasuo ; Arinobu, Yojiro ; Tsuzuki, Hirofumi ; Kikushige, Yoshikane ; Iino, Tadafumi ; Kato, Koji ; Takenaka, Katsuto ; Miyamoto, Toshihiro ; Maeda, Takahiro ; Akashi, Koichi. / Identification of unipotent megakaryocyte progenitors in human hematopoiesis. :: Blood. 2017 ; 巻 129, 番号 25. pp. 3332-3343.
@article{316d42564cdd4e0496c6177c8aa6a351,
title = "Identification of unipotent megakaryocyte progenitors in human hematopoiesis",
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).",
author = "Kohta Miyawaki and Hiromi Iwasaki and Takashi Jiromaru and Hirotake Kusumoto and Ayano Yurino and Takeshi Sugio and Yasufumi Uehara and Jun Odawara and Shinya Daitoku and Yuya Kunisaki and Yasuo Mori and Yojiro Arinobu and Hirofumi Tsuzuki and Yoshikane Kikushige and Tadafumi Iino and Koji Kato and Katsuto Takenaka and Toshihiro Miyamoto and Takahiro Maeda and Koichi Akashi",
year = "2017",
month = "6",
day = "22",
doi = "10.1182/blood-2016-09-741611",
language = "English",
volume = "129",
pages = "3332--3343",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "25",

}

TY - JOUR

T1 - Identification of unipotent megakaryocyte progenitors in human hematopoiesis

AU - Miyawaki, Kohta

AU - Iwasaki, Hiromi

AU - Jiromaru, Takashi

AU - Kusumoto, Hirotake

AU - Yurino, Ayano

AU - Sugio, Takeshi

AU - Uehara, Yasufumi

AU - Odawara, Jun

AU - Daitoku, Shinya

AU - Kunisaki, Yuya

AU - Mori, Yasuo

AU - Arinobu, Yojiro

AU - Tsuzuki, Hirofumi

AU - Kikushige, Yoshikane

AU - Iino, Tadafumi

AU - Kato, Koji

AU - Takenaka, Katsuto

AU - Miyamoto, Toshihiro

AU - Maeda, Takahiro

AU - Akashi, Koichi

PY - 2017/6/22

Y1 - 2017/6/22

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=85021635830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021635830&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-09-741611

DO - 10.1182/blood-2016-09-741611

M3 - Article

C2 - 28336526

AN - SCOPUS:85021635830

VL - 129

SP - 3332

EP - 3343

JO - Blood

JF - Blood

SN - 0006-4971

IS - 25

ER -