Details

Autor(en) / Beteiligte

• Wei, Yanchang
• Yang, Cai-Rong
• Zhao, Zhen-Ao

Titel

Viable offspring derived from single unfertilized mammalian oocytes

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2022-03, Vol.119 (12), p.e2115248119-e2115248119

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• In mammals, a new life starts with the fusion of an oocyte and asperm cell. Parthenogenesis, a way of generating offspring solelyfrom female gametes, is limited because of problems arising fromgenomic imprinting. Here, we report live mammalian offspringderived from single unfertilized oocytes, which was achieved by tar-geted DNA methylation rewriting of seven imprinting control regions.Oocyte coinjection of catalytically inactive Cas9 (dCas9)-Dnmt3a ordCpf1-Tet1 messenger RNA (mRNA) with single-guide RNAs (sgRNAs)targeting specific regions induced de novo methylation or demethyla-tion, respectively, of the targeted region. Following parthenogeneticactivation, these edited regions showed maintenance of methylationas naturally established regions during early preimplantation develop-ment. The transfer of modified parthenogenetic embryos into fostermothers resulted in significantly extended development andfinally inthe generation of viable full-term offspring. These data demonstratethat parthenogenesis can be achieved by targeted epigenetic rewrit-ing of multiple critical imprinting control regions.