Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells

Clifford Z Liu; Aditi Prasad; Bharati Jadhav; Yu Liu; Mingxia Gu; Andrew J Sharp; Bruce D Gelb

doi:10.1016/j.isci.2023.108599

Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells

iScience. 2023 Nov 30;27(1):108599. doi: 10.1016/j.isci.2023.108599. eCollection 2024 Jan 19.

Authors

Clifford Z Liu^{1

2}, Aditi Prasad^{1

2}, Bharati Jadhav^{1

3}, Yu Liu⁴, Mingxia Gu^{4

5

6

7}, Andrew J Sharp^{1

3}, Bruce D Gelb^{1

3

8}

Affiliations

¹ Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ Department of Medicine, Division of Cardiovascular Medicine, Stanford School of Medicine, Stanford, CA, USA.
⁵ Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶ Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
⁷ Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁸ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

Valvular heart disease presents a significant health burden, yet advancements in valve biology and therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells, which are transcriptionally and phenotypically distinct from vascular endothelial cells. These endocardial cells can be challenged to undergo endothelial-to-mesenchymal transition (EndMT), after which two distinct populations emerge-one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). We then characterized these populations through bulk RNA-seq transcriptome analyses and compared our VIC and VEC populations to pseudobulk data generated from normal valve tissue of a 15-week-old human fetus. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease.

Keywords: Biological sciences; Cardiology; Developmental biology; Stem cell research.

Abstract

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