Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow
Zixian Liu,
Jinhong Wang,
Yao Ma,
Miner Xie,
Peng Wu,
Sen Zhang,
Xiaofang Wang,
Fang Dong,
Hui Cheng,
Ping Zhu,
Mingzhe Han,
Hideo Ema
Affiliations
Zixian Liu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Jinhong Wang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Yao Ma
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Miner Xie
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Peng Wu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Sen Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Xiaofang Wang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Fang Dong
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Hui Cheng
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Ping Zhu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Mingzhe Han
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Hideo Ema
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201−CD48− cells and CD48+ cells separated from the CD150+CD34−Kit+Sca-1+Lin− HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.
