Generation of blastoids from human parthenogenetic stem cells

Author:

Zhong Ke12,Luo Yu-Xin23,Li Dan4,Min Zhe-Ying1,Fan Yong1ORCID,Yu Yang234ORCID

Affiliation:

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

2. 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

3. National Clinical Research Center for Obstetrics and Gynecology , Beijing 100191 , China

4. Clinical Stem Cell Research Center, Peking University Third Hospital , Beijing 100191 , China

Abstract

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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

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