Generation of Genetically Identical Mammalian Oocytes from Parthenogenetic Double-Haploid Embryonic Stem Cells

Lin, J.; Zou, G.; Wei, S.; Zhang, Y.; Dingrui, G.; Li, S.; Hu, M.; Du, J.; Wang, W.; Jamal, M. A.; Bao, W.; Zhou, C.; Kang, X.; Bian, S.

doi:10.64898/2026.04.04.716050

bioRxiv · 10.64898/2026.04.04.716050

Generation of Genetically Identical Mammalian Oocytes from Parthenogenetic Double-Haploid Embryonic Stem Cells

Lin, J.·Zou, G.·Wei, S.·Zhang, Y.·Dingrui, G.·Li, S.·Hu, M.·Du, J.·Wang, W.·Jamal, M. A.·Bao, W.·Zhou, C.·Kang, X.·Bian, S.

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Abstract

Generating genetically identical mammalian oocytes is challenging due to stochastic meiotic recombination. Here, we established parthenogenetic double-haploid embryonic stem cells (PG-DhESCs) possessing complete homozygosity. By employing blastocyst complementation in Prdm14-deficient embryos, we generated chimeric females that produced oocytes derived exclusively from these donor cells. Fertilization of these oocytes yielded viable, fertile, maternally semi-cloned (MSC) mice of both sexes. Although DNA methylation was largely restored during gametogenesis, subtle epigenetic defects correlated with increased body weight in MSC offspring. This study establishes a robust platform combining PG-DhESCs with blastocyst complementation to generate isogenic mammalian oocytes, overcoming traditional limitations in mammalian cloning.

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Lin, J., Zou, G., Wei, S., Zhang, Y., Dingrui, G., Li, S., Hu, M., Du, J., Wang, W., Jamal, M. A., Bao, W., Zhou, C., Kang, X., Bian, S.. 2026-04-07. Generation of Genetically Identical Mammalian Oocytes from Parthenogenetic Double-Haploid Embryonic Stem Cells. https://doi.org/10.64898/2026.04.04.716050

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