- Soncin, Francesca;
- Morey, Robert;
- Bui, Tony;
- Requena, Daniela F;
- Cheung, Virginia Chu;
- Kallol, Sampada;
- Kittle, Ryan;
- Jackson, Madeline G;
- Farah, Omar;
- Chousal, Jennifer;
- Meads, Morgan;
- Pizzo, Donald;
- Horii, Mariko;
- Fisch, Kathleen M;
- Parast, Mana M
Trophoblast stem cells (TSCs) have recently been derived from human embryos and early-first-trimester placenta; however, aside from ethical challenges, the unknown disease potential of these cells limits their scientific utility. We have previously established a bone morphogetic protein 4 (BMP4)-based two-step protocol for differentiation of primed human pluripotent stem cells (hPSCs) into functional trophoblasts; however, those trophoblasts could not be maintained in a self-renewing TSC-like state. Here, we use the first step from this protocol, followed by a switch to newly developed TSC medium, to derive bona fide TSCs. We show that these cells resemble placenta- and naive hPSC-derived TSCs, based on their transcriptome as well as their in vitro and in vivo differentiation potential. We conclude that primed hPSCs can be used to generate functional TSCs through a simple protocol, which can be applied to a widely available set of existing hPSCs, including induced pluripotent stem cells, derived from patients with known birth outcomes.