从人类孤雌生殖干细胞中产生囊胚

Life medicine Pub Date : 2023-02-18 eCollection Date: 2023-02-01 DOI:10.1093/lifemedi/lnad006
Ke Zhong, Yu-Xin Luo, Dan Li, Zhe-Ying Min, Yong Fan, Yang Yu
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引用次数: 0

摘要

孤雌生殖胚胎的基因组完全来自母亲的基因组,缺乏父亲的印记模式。利用人类孤雌胚胎干细胞(hPg-ESCs)进行基因组印迹的研究取得了许多成果。然而,由于发育缺陷和伦理限制,对孤雌胚胎发育仍缺乏全面的认识。在这里,我们使用我们之前发表的两步诱导方案,从hpg - esc衍生的扩展多能干细胞(hPg-EPSCs)中生成了孤雌生殖囊胚(hPg-EPSCs囊胚)。形态学、特异性标记表达和单细胞转录组分析表明,hPg-EPSCs囊胚具有与人类双亲本EPSCs (hBp-EPSCs)产生的囊胚(hBp-EPSCs囊胚)相似的关键细胞系。单细胞RNA-seq比较了hPg-EPSCs囊胚和hBp-EPSCs囊胚中印迹和X染色体失活相关基因的表达。总之,我们获得了单性生殖囊胚,这将有可能促进基因组印迹在胚胎发育中的研究,揭示亲本起源偏见对人类发育的影响及其病理机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Generation of blastoids from human parthenogenetic stem cells.

Parthenogenetic embryos derive their genomes entirely from the maternal genome and lack paternal imprint patterns. Many achievements have been made in the study of genomic imprinting using human parthenogenetic embryonic stem cells (hPg-ESCs). However, due to developmental defects and ethical limits, a comprehensive understanding of parthenogenetic embryonic development is still lacking. Here, we generated parthenogenetic blastoids (hPg-EPSCs blastoids) from hPg-ESC-derived extended pluripotent stem cells (hPg-EPSCs) using our previously published two-step induction protocol. Morphology, specific marker expression and single-cell transcriptome analysis showed that hPg-EPSCs blastoids contain crucial cell lineages similar to blastoids (hBp-EPSCs blastoids) generated from human biparental EPSCs (hBp-EPSCs). Single-cell RNA-seq compared the expression of genes related to imprinting and X chromosome inactivation in hPg-EPSCs blastoids and hBp-EPSCs blastoids. In conclusion, we generated parthenogenetic blastoids, which will potentially promote the study of genomic imprinting in embryonic development and uncover the influence of parental origin bias on human development and pathological mechanisms.

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