Selective Differentiation into Hematopoietic and Cardiac Cells from Pluripotent Stem Cells Based on the Expression of

Atsumasa Okada1, Katsuhisa Tashiro1, Tomoko Yamaguchi1

  • 1Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.

Insights

Coxsackie and adenovirus receptor (CAR) effectively separates pluripotent stem cell-derived Flk1(+) mesodermal cells. This novel marker distinguishes hematopoietic and cardiac progenitors, enabling efficient cell generation.

Area of Science:

  • Stem cell biology
  • Developmental biology
  • Cell biology

Background:

  • Flk1-expressing mesodermal cells are crucial for generating hematopoietic cells and cardiomyocytes from pluripotent stem cells (PSCs).
  • However, Flk1(+) cells are heterogeneous, containing both hematopoietic and cardiac progenitors.
  • Efficiently separating these progenitors is essential for directed differentiation.

Purpose of the Study:

  • To identify a novel cell surface marker for efficient separation of PSC-derived Flk1(+) mesodermal progenitors.
  • To establish a method for highly efficient production of hematopoietic cells and cardiomyocytes from PSCs.

Main Methods:

  • Utilized coxsackievirus and adenovirus receptor (CAR) expression to stratify Flk1(+) cells.
  • Separated mouse and human PSC- and mouse embryo-derived Flk1(+) cells into Flk1(+)CAR(-) and Flk1(+)CAR(+) populations.
  • Assessed the differentiation potential of separated cell populations into hematopoietic cells and cardiomyocytes.

Main Results:

  • CAR expression successfully divided Flk1(+) cells into two distinct populations: Flk1(+)CAR(-) and Flk1(+)CAR(+).
  • Flk1(+)CAR(-) cells efficiently differentiated into hematopoietic cells.
  • Flk1(+)CAR(+) cells efficiently differentiated into cardiomyocytes.

Conclusions:

  • Coxsackie and adenovirus receptor (CAR) is a novel and effective cell surface marker for distinguishing hematopoietic and cardiac progenitors within Flk1(+) mesodermal cells.
  • CAR-based separation enables a highly efficient differentiation method from PSCs into specific hematopoietic and cardiac lineages.
  • This finding provides a valuable tool for regenerative medicine and cell-based therapies.

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