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Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs
bioRxiv - Synthetic Biology Pub Date : 2021-01-25 , DOI: 10.1101/2021.01.25.428068
Jan Langkabel , Arik Horne , Lorenzo Bonaguro , Tatiana Hesse , Alexej Knaus , Yannick Riedel , Kristian Händler , Kevin Bassler , Nico Reusch , Leon Harootoonovtch Yeghiazarian , Tal Pecht , Anna C. Aschenbrenner , Franziska Kaiser , Caroline Kubaczka , Joachim L. Schultze , Hubert Schorle

Blastocyst derived stem cell lines were shown to selforganize into embryo like structures in 3D cell culture environments. Here, we provide evidence that synthetic embryo like structures are generated solely based on transcription factor mediated molecular reprogramming of embryonic stem cells in a simple 3D co culture system. ESCs in these cultures selforganize into elongated, compartmentalized synthetic embryo like structures over the course of reprogramming exhibiting anterior visceral endoderm formation and symmetry breaking. Single cell RNA Seq reveals transcriptional profiles resembling epiblast, visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5 to E5.5. Within the epiblast, compartment marker gene expression supports primordial germ cell specification. After transplantation, synthetic embryo like structures implant in uteri and initiate the formation of decidual tissues. This system allows for fast and reproducible generation of synthetic embryo like structures, providing further insights into synthetic embryology.

中文翻译:

使用ESCs中的重编程范例诱导植入期周围的合成胚胎

胚泡衍生的干细胞系在3D细胞培养环境中显示出自组织成胚状结构的能力。在这里,我们提供的证据表明,仅在简单的3D共培养系统中,仅基于转录因子介导的胚胎干细胞分子重编程即可生成合成的胚胎样结构。在重新编程过程中,这些培养物中的ESC自组织成细长的,分隔的合成胚胎样结构,显示出内脏内胚层的形成和对称性的破坏。单细胞RNA Seq揭示了类似于E4.5至E5.5早期鼠胚的上皮细胞,内脏内胚层和胚外外胚层的转录特征。在上皮细胞中,区室标记基因表达支持原始生殖细胞规格。移植后 人造胚样结构植入子宫并启动蜕膜组织的形成。该系统允许快速且可重现的合成胚胎样结构生成,为合成胚胎学提供了进一步的见识。
更新日期:2021-01-26
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