在开发的第一周,人类胚胎形成由内部细胞团和滋养外胚层(TE)细胞组成的胚泡,后者是胎盘滋养层的祖细胞。这里,我们研究了从胚泡早期到晚期的人TE中转录本的表达。我们鉴定了转录因子GATA2,GATA3,TFAP2C和KLF5的富集,并表征了它们在TE发育过程中的蛋白质表达动力学。通过诱导型过表达和mRNA转染,我们确定这些因素,和MYC一起,足以从引发的人胚胎干细胞建立诱导的滋养层干细胞(iTSC)。这些iTSCs自我更新并概括了形态学特征,基因表达谱,和定向分化潜力,与现有的人类TSC相似。每个系统的遗漏,或多种因素的组合,揭示了GATA2和GATA3对iTSC转分化的重要性。总之,这些发现提供了对可能在人类TE中起作用的转录因子网络的见解,并拓宽了建立早期人类胎盘祖细胞细胞模型的方法,这可能在未来对胎盘相关疾病的模型是有用的。
During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development. By inducible overexpression and mRNA transfection, we determined that these factors, together with MYC, are sufficient to establish induced trophoblast stem cells (iTSCs) from primed human embryonic stem cells. These iTSCs self-renew and recapitulate morphological characteristics, gene expression profiles, and directed differentiation potential, similar to existing human TSCs. Systematic omission of each, or combinations of factors, revealed the crucial importance of GATA2 and GATA3 for iTSC transdifferentiation. Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases.