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Title: Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions
Author: Zhi-Kun Li, Le-Yun Wang, Li-Bin Wang, Gui-Hai Feng, Xue-Wei Yuan, Chao Liu, Kai Xu, Yu-Huan Li, Hai-Feng Wan, Ying Zhang, Yu-Fei Li, Xin Li, Wei Li, Qi Zhou, Bao-Yang Hu

Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, bipaternal reproduction has not been previously achieved in mammals. We found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells. Through MII oocyte injection or sperm coinjection with hypomethylated haploid ESCs carrying specific imprinted region deletions, we obtained live bimaternal and bipaternal mice. Deletion of 3 imprinted regions in parthenogenetic haploid ESCs restored normal growth of fertile bimaternal mice, whereas deletion of 7 imprinted regions in androgenetic haploid ESCs enabled production of live bipaternal mice that died shortly after birth. Phenotypic analyses of organ and body size of these mice support the genetic conflict theory of genomic imprinting. Taken together, our results highlight the factors necessary for crossing same-sex reproduction barriers in mammals.

Corresponding author: Wei Li, Qi Zhou, Bao-Yang Hu
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PubYear: 2018
Issue: DOI: 10.1016/j.stem.2018.09.004
Journal: Cell Stem Cell
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URL: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30441-7