Early Megakaryocyte Lineage-committed Progenitors in Adult Mouse Bone Marrow

Overview

Journal Blood Sci

Date 2024 May 9

PMID 38721470

Authors

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

Soon will be listed here.

Abstract

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 CD201CD48 cells and CD48 cells separated from the CD150CD34KitSca-1Lin 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.

Citing Articles

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