Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells

Cell
Xin LiQi Zhou

Abstract

Mammalian interspecific hybrids provide unique advantages for mechanistic studies of speciation, gene expression regulation, and X chromosome inactivation (XCI) but are constrained by their limited natural resources. Previous artificially generated mammalian interspecific hybrid cells are usually tetraploids with unstable genomes and limited developmental abilities. Here, we report the generation of mouse-rat allodiploid embryonic stem cells (AdESCs) by fusing haploid ESCs of the two species. The AdESCs have a stable allodiploid genome and are capable of differentiating into all three germ layers and early-stage germ cells. Both the mouse and rat alleles have comparable contributions to the expression of most genes. We have proven AdESCs as a powerful tool to study the mechanisms regulating X chromosome inactivation and to identify X inactivation-escaping genes, as well as to efficiently identify genes regulating phenotypic differences between species. A similar method could be used to create hybrid AdESCs of other distantly related species.

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Citations

Apr 23, 2016·Trends in Genetics : TIG·Bradley P Balaton, Carolyn J Brown
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tian-Da LiQi Zhou
Oct 21, 2016·Nature Protocols·Ido SagiNissim Benvenisty
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May 17, 2021·Reproduction in Domestic Animals = Zuchthygiene·Gerelchimeg BouZhonghua Liu
Sep 13, 2021·Development, Growth & Differentiation·Xun HuangAnming Meng

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