RESUMEN
A limited number of accessible and representative models of human trophoblast cells currently exist for the study of placentation. Current stem cell models involve either a transition through a naïve stem cell state or precise dynamic control of multiple growth factors and small-molecule cues. Here, we demonstrated that a simple five-day treatment of human induced pluripotent stem cells with two small molecules, retinoic acid (RA) and Wnt agonist CHIR 99021 (CHIR), resulted in rapid, synergistic upregulation of CDX2. Transcriptomic analysis of RA + CHIR-treated cells showed high similarity to primary trophectoderm cells. Multipotency was verified via further differentiation towards cells with syncytiotrophoblast or extravillous trophoblast features. RA + CHIR-treated cells were also assessed for the established criteria defining a trophoblast cell model, and they possess all the features necessary to be considered valid. Collectively, our data demonstrate a facile, scalable method for generating functional trophoblast-like cells in vitro to better understand the placenta.
Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Tretinoina , Trofoblastos , Humanos , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , Trofoblastos/citología , Tretinoina/farmacología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Piridinas/farmacología , Femenino , Factor de Transcripción CDX2/metabolismo , Factor de Transcripción CDX2/genética , Pirimidinas/farmacología , Embarazo , Modelos Biológicos , Células CultivadasRESUMEN
Progress in deriving a spectrum of central nervous system cell phenotypes from human pluripotent stem cells has spurred significant advances in in vitro modeling and development of regenerative therapies for neurological disorders. While the clinical impact of these advances is still being evaluated, their integration with advanced tissue engineering methodologies and therapeutic approaches that induce neural circuit plasticity, respectively, remain underexplored frontiers.