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Isolation of Murine Embryonic Hemogenic Endothelial Cells
Published on: June 17, 2016
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Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression
Patrick Coulombe1,2, Grace Cole1,3, Amanda Fentiman1,4
1Michael Smith Genome Sciences Centre, BC Cancer, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.
Nature Communications
|July 27, 2023
Summary
Meis1 is a key transcription factor essential for specifying hemogenic endothelial cells during early development. Its role is critical for the endothelial-to-hematopoietic transition and the subsequent emergence of hematopoietic stem and progenitor cells.
Area of Science:
- Developmental Biology
- Hematopoiesis
- Cell Biology
Background:
- Hematopoietic stem and progenitor cells (HSPCs) arise from hemogenic endothelial (HE) cells via endothelial-to-hematopoietic transition (EHT).
- Understanding the molecular drivers of HE cell specification is crucial for defining cells capable of EHT.
Purpose of the Study:
- To characterize early pre-HE cell subpopulations using integrated transcriptomic and surface marker data.
- To identify key regulators involved in hemogenic cell specification prior to Runx1 expression.
Main Methods:
- Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) was employed to define pre-HE cells.
- Analysis of transcription factor expression and function, including Meis1, in endothelial cells during embryogenesis.
Main Results:
- Meis1 was identified as an essential transcription factor for hemogenic cell specification, preceding Runx1 expression.
- Meis1 expression distinguishes pre-HE cells committed to hematopoiesis from arterial endothelial cells.
- Conditional deletion of Meis1 in endothelial cells impaired the development of functional HE cells and subsequent HSPC emergence.
Conclusions:
- Meis1 plays a critical role in the early specification of endothelial cells towards a hemogenic fate.
- Meis1 is implicated in a crucial fate-determining step that establishes EHT potential in endothelial cells.
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