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Induction of trophoblast stem cells from human pluripotent stem cells [ATAC-seq]

ABSTRACT: In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE135693 | GEO | 2021/08/16

REPOSITORIES: GEO

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