Cell Stem Cell
Volume 28, Issue 3, 4 March 2021, Pages 535-549.e8
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Decoding Human Megakaryocyte Development

https://doi.org/10.1016/j.stem.2020.11.006Get rights and content
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Highlights

  • A comprehensive single-cell transcriptomic landscape of human MKs is constructed

  • MKs show cellular heterogeneity with distinct metabolic and cell cycle signatures

  • CD14+ MKs with immune characteristics are generated along a distinct trajectory

  • THBS1 is identified as an early marker for MK-biased endothelial cells from hESCs

Summary

Despite our growing understanding of embryonic immune development, rare early megakaryocytes (MKs) remain relatively understudied. Here we used single-cell RNA sequencing of human MKs from embryonic yolk sac (YS) and fetal liver (FL) to characterize the transcriptome, cellular heterogeneity, and developmental trajectories of early megakaryopoiesis. In the YS and FL, we found heterogeneous MK subpopulations with distinct developmental routes and patterns of gene expression that could reflect early functional specialization. Intriguingly, we identified a subpopulation of CD42b+CD14+ MKs in vivo that exhibit high expression of genes associated with immune responses and can also be derived from human embryonic stem cells (hESCs) in vitro. Furthermore, we identified THBS1 as an early marker for MK-biased embryonic endothelial cells. Overall, we provide important insights and invaluable resources for dissection of the molecular and cellular programs underlying early human megakaryopoiesis.

Keywords

single-cell RNA sequencing
yolk sac
fetal liver
megakaryopoiesis
megakaryocyte
platelets
human embryonic stem cells
THBS1

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These authors contributed equally

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