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Reprogramming Epiblast Stem Cells into Pre-Implantation Blastocyst Cell-like Cells
bioRxiv - Synthetic Biology Pub Date : 2020-10-01 , DOI: 10.1101/2020.09.29.318279
Kiichiro Tomoda , Haiming Hu , Yoshiki Sahara , Hashimita Sanyal , Minoru Takasato , Cody Kime

Recently, a new wave of synthetic embryo systems (SESs) have been established from cultured cells toward efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected microscopically. Here, we further explored the system over key time points with unprecedented single-cell RNA sequencing (scRNA-seq) analysis and revealed broad induction of the 2C-like reporter MERVL and RNA velocity diverging three major population regions with genetic expression resembling pluripotent epiblast (EPI), primitive endoderm (PE), and trophectoderm (TE). Enrichment of those three BC-like cell fates involved key regulons, zygotic genome activation (ZGA) related genes, specific RNA splicing, and select cells meaningfully distinguished critical regulons of model cells. This analysis confirms the induction of the extraembryonic cell populations during the reprogramming and we anticipate that our unique BCLH SES and rich data may uncover new facets of cell potency, improve developmental biology, and help biomedicine advance.

中文翻译:

重新编程成胚前干细胞样细胞成胚干细胞。

最近,从培养细胞向有效和符合道德的胚胎发育研究建立了新的合成胚胎系统(SESs)浪潮。最近,我们报道了我们的表皮干细胞(EPISC)重编程SES,该SES生成了许多囊胚(BC)样半球(BCLH),并在显微镜下检测到了多能和胚外细胞特征。在这里,我们通过空前的单细胞RNA测序(scRNA-seq)分析在关键时间点进一步探索了该系统,并揭示了2C样报道分子MERVL的广泛诱导和RNA速度使三个主要人群区域发生了分化,其基因表达类似于多能表皮细胞( EPI),原始内胚层(PE)和滋养外胚层(TE)。这三种BC样细胞命运的富集涉及关键调控因子,合子基因组激活(ZGA)相关基因,特异性RNA剪接,并选择有意义地区分模型单元的关键规则的单元。该分析证实了重编程过程中胚胎外细胞群的诱导,并且我们预期我们独特的BCLH SES和丰富的数据可能会揭示细胞效能的新方面,改善发育生物学,并帮助生物医学发展。
更新日期:2020-10-02
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