Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access to human embryos and first-trimester placentas is limited, thus preventing the establishment of hTSCs from diverse genetic backgrounds associated with placental disorders. Here, we show that hTSCs can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (1) somatic cell reprogramming of adult fibroblasts with OCT4, SOX2, KLF4, MYC (OSKM) and (2) cell fate conversion of naive and extended pluripotent stem cells. The resulting induced/converted hTSCs recapitulated hallmarks of hTSCs including long-term self-renewal, expression of specific transcription factors, transcriptomic signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSCs and show that these cells resemble day 8 cytotrophoblasts. Altogether, hTSC lines of diverse genetic origins open the possibility to model both placental development and diseases in a dish. [Display omitted] •Reprogramming of patient somatic cells to induced hTSCs with OSKM•Conversion of naive and extended hPSCs to hTSCs•Comparison of models of the human trophoblast lineage•h(i/c)TSCs are akin to day 8 trophoblasts of the human embryo Castel et al. report the generation of patient-specific human induced trophoblast stem cells via two methods: (1) somatic cell reprogramming with OSKM and (2) conversion of naive and extended hiPSCs. Their findings open avenues to study placental diseases and relations between the trophoblast lineage, pluripotency, and the human embryo.