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APLNR marks a cardiac progenitor derived with human induced pluripotent stem cells

Yin-Yu Lam1, Chun-Ho Chan1, Lin Geng2

  • 1Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.

Heliyon
|August 4, 2023
PubMed

Insights

Researchers identified APLNR as a novel surface marker to isolate cardiac progenitors from human induced pluripotent stem cells (hiPSCs). This method improves the consistency of generating cardiomyocytes for cardiac research and regeneration.

Area of Science:

  • Stem Cell Biology
  • Developmental Biology
  • Cardiovascular Research

Background:

  • Generating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) shows variable efficiency across different cell lines and batches.
  • Inconsistencies in in vitro cardiac differentiation hinder reliable applications in disease modeling and regenerative medicine.

Purpose of the Study:

  • To identify reliable markers for isolating cardiac progenitor cells during hiPSC differentiation.
  • To develop a robust platform for generating cardiomyocytes from diverse hiPSC lines with improved consistency.

Main Methods:

  • Single-cell transcriptomics was employed on hiPSCs during cardiac differentiation to map cell lineages.
  • APLNR was identified as a surface marker for cardiac progenitors, which were then isolated using immunomagnetic separation.
  • Transcriptomic analysis was performed on isolated APLNR+ cardiac progenitors and compared with in vivo embryonic datasets.

Main Results:

  • Single-cell transcriptomics revealed distinct cardiac and extra-cardiac lineages during hiPSC differentiation.
  • APLNR+ cells were identified as a specific population of in vitro cardiac progenitors.
  • Differentiation of isolated APLNR+ progenitors yielded predominantly cardiomyocytes and cardiac mesenchyme, with transient progenitor marker expression.
  • APLNR expression was validated in early cardiac progenitors in human and mouse embryos.

Conclusions:

  • APLNR serves as a reliable surface marker for isolating in vitro cardiac progenitors from multiple hiPSC lines without genetic modification.
  • This platform offers a consistent method for generating cardiomyocytes and cardiac mesenchyme, applicable to cardiac development studies, disease modeling, and regenerative medicine.
  • The findings provide a foundation for more predictable and scalable cardiomyocyte production from stem cells.

Keywords:
Cardiac stem cell biologyInduced pluripotent stem cellsPluripotent stem cell derived cardiomyocytesStem cell differentiation

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