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从人孤雌生殖干细胞生成囊胚样细胞。

Generation of blastoids from human parthenogenetic stem cells.

作者信息

Zhong Ke, Luo Yu-Xin, Li Dan, Min Zhe-Ying, Fan Yong, Yu Yang

机构信息

Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

Department of Obstetrics and Gynecology, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.

出版信息

Life Med. 2023 Feb 18;2(1):lnad006. doi: 10.1093/lifemedi/lnad006. eCollection 2023 Feb.

Abstract

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.

摘要

孤雌生殖胚胎的基因组完全来自母本基因组,缺乏父本印记模式。利用人类孤雌生殖胚胎干细胞(hPg-ESCs)在基因组印记研究方面已取得许多成果。然而,由于发育缺陷和伦理限制,对孤雌生殖胚胎发育仍缺乏全面了解。在此,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样结构(hPg-EPSCs囊胚样结构)。形态学、特异性标志物表达和单细胞转录组分析表明,hPg-EPSCs囊胚样结构包含与人类双亲EPSCs(hBp-EPSCs)产生的囊胚样结构(hBp-EPSCs囊胚样结构)相似的关键细胞谱系。单细胞RNA测序比较了hPg-EPSCs囊胚样结构和hBp-EPSCs囊胚样结构中与印记和X染色体失活相关基因的表达。总之,我们生成了孤雌生殖囊胚样结构,这可能会促进胚胎发育中基因组印记的研究,并揭示亲本来源偏差对人类发育和病理机制的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4656/11748981/0a1159a6d488/lnad006_fig1.jpg

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