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Related Experiment Video

Updated: Jan 3, 2026

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Single cell transcriptome dynamics from pluripotency to FLK1+ mesoderm.

Haiyong Zhao1, Kyunghee Choi2

  • 1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

Development (Cambridge, England)
|November 20, 2019
PubMed
Summary

Researchers mapped the continuous development of hemangiogenic progenitors from mouse embryonic stem cells. Smooth muscle appears to be the default fate of FLK1-expressing mesoderm, guided by transcription factors.

Keywords:
Etv2Flk1/KdrHemangiogenesisMouse embryonic stemSingle cell RNA sequencingVascular smooth muscleYolk sac

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Transcriptomics

Background:

  • Hemangiogenic progenitors, crucial for blood and endothelial cells, arise from FLK1-expressing (FLK1+) mesoderm, regulated by the transcription factor ETV2.
  • FLK1+ mesoderm also contributes to smooth muscle and cardiomyocytes, but its generation and cell fate allocation processes are not fully understood.
  • Existing single-cell RNA sequencing studies offer static snapshots, lacking insights into continuous dynamic developmental processes.

Purpose of the Study:

  • To capture and analyze the continuous developmental process of hemangiogenesis from *in vitro*-differentiated mouse embryonic stem (ES) cells.
  • To elucidate the developmental trajectory of FLK1+ mesoderm and its allocation to various cell fates.
  • To identify key transcription factors and signaling pathways involved in hemangiogenesis and mesoderm differentiation.

Main Methods:

  • Performed single-cell RNA sequencing (scRNA-seq) on *in vitro*-differentiated mouse ES cells.
  • Analyzed the temporal gene expression dynamics to reconstruct continuous developmental pathways.
  • Utilized bioinformatic approaches to identify transcription factor modules and regulatory networks.

Main Results:

  • Hemangiogenic progenitors develop through intermediate gastrulation stages, specified by overlapping transcription factor modules in a 'relay'-like manner.
  • The transcriptional program of FLK1+ mesoderm is maintained in the smooth muscle lineage, suggesting smooth muscle as the default fate.
  • SRC kinase was identified as a contributor to ETV2-mediated activation of the hemangiogenic program.

Conclusions:

  • This study provides a continuous transcriptome map of hemangiogenesis from ES cells, offering dynamic insights into mesoderm development.
  • The findings suggest a default smooth muscle fate for FLK1+ mesoderm and highlight the role of sequential transcription factor activity.
  • The generated map serves as a valuable resource for future research in basic and applied mesoderm development studies.