Direct Reprogramming of Human Fibroblasts into Fully Functional Trophoblast Stem Cells

Trophoblast stem cells (TSCs), equivalent to first-trimester cytotrophoblasts, serve as valuable models for studying placental diseases and understanding early embryogenesis. Recent studies have demonstrated that human-induced trophoblast stem cells (hiTSCs) can be generated either by overexpressing the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) in fibroblasts or through the transdifferentiation of pluripotent stem cells. In this chapter, we describe a methodology for directly converting fibroblasts into fully functional hiTSCs using the transcription factors GATA3, OCT4, KLF4, and MYC (GOKM). This approach circumvents the need for inducing full pluripotency and avoids the expression of pluripotency factors per se. Moreover, the GOKM method seems to be superior technique, as it yields high number of colonies and a transcriptomic profile closely resembling blastocyst/first trimester-derived TSCs.