U.S. Department of Health and Human ServicesHHS National Institutes of HealthNIH National Center for Advancing Translational SciencesNCATS

Controlled, Efficient Differentiation of Human Pluripotent Stem Cells Into Proliferative Trophoblast

Posted on June 24th, 2020 by claire.malley@nih.gov

Members of SCTL presented a poster at ISSCR 2020 Virtual. The poster is entitled: Controlled, Efficient Differentiation of Human Pluripotent Stem Cells Into Proliferative Trophoblast.

Authors (underlined, presenting): Jaroslav Slamecka, Carlos Tristan, Tao Deng, Pei-Hsuan Chu, Claire Malley, Joseph Ernest, Princy Francis, Vukasin Jovanovic, Seung Mi Ryu, Jason Inman, Hyen Jong Hong, Pinar Ormanoglu, Elena Barnaeva, Yeliz Gedik, Anton Simeonov, Ilyas Singec╠ž

Download the full-size poster here.

More information about ISSCR 2020 Virtual.

Abstract

The in vivo embryonic counterpart of cultured human pluripotent stem cells (hPSCs) are presumably the cells of the post- implantation epiblast, with a capacity restricted to giving rise to the embryo proper and no longer able to develop into trophectoderm (TE). Previous studies that reported TE differentiation from hPSCs remain controversial, in part due to incomplete differentiation or the use of undefined culture conditions. Here we describe highly efficient TE differentiation, followed by fusion of a subset of cells into multi-nucleated syncytiotrophoblast cells, in chemically defined conditions. Gene expression profiling by bulk and single-cell RNA-seq, and immunocytochemical analysis confirmed robust and step-wise induction of genes associated with trophectoderm and placental development, such as GATA3, IGFBP3, KRT7, CDX2, followed by CGA, DAB2, TEAD3, DLX3, expressed in fused multi-nucleated cells. We then developed a chemically defined medium that supported stable and long-term self-renewal of cell lines established from both hESC- and hiPSC- differentiated TE cells while maintaining molecular features associated with trophoblast. These in vitro-generated proliferating trophoblast cells may prove ideal for modeling diseases of the placenta, drug screening, and cell-based therapies.