title: Roles of CDX2 and EOMES in human induced trophoblast progenitor cells.
abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, can be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and EOMES may play critical roles in human iTP cell generation.
authors: Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA. ying.chen@hc.msu.edu
authors: Ying
authors: Y
authors: Chen
authors: Kai
authors: K
authors: Wang
authors: Yun Guo
authors: YG
authors: Gong
authors: Sok Kean
authors: SK
authors: Khoo
authors: Richard
authors: R
authors: Leach
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D044127:Epigenesis, Genetic; D004958:Estradiol / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D020825:T-Box Domain Proteins / Q000502:physiology*; D059467:Transcriptome; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D006063:Chorionic Gonadotropin; C491199:EOMES protein, human; D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; D004958:Estradiol