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Dissection of uniparental reproduction barriers in mice using haploid embryonic stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE120039 | GEO | 2018/10/11

REPOSITORIES: GEO

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Dissection of uniparental reproduction barriers in mice using haploid embryonic stem cells [RRBS]

Project description:Uniparental reproduction is widespread among lower vertebrates, but not in mammals. Researchers have produced bimaternal mice with a deletion of the H19 imprinted region. However, the mechanism of a single deletion in an immature oocyte sufficient to cross uniparental barriers is unknown. We found bimaternal-derived mice to be defective in multiple aspects. More importantly, bipaternal reproduction has not been achieved in mammals. Thus, the barrier of uniparental reproduction in mammals has not been elucidated. We identified a DNA hypomethylation status in haploid embryonic stem cells similar to that in primordial germ cells, with which bimaternal and bipaternal mice can be obtained by injection of haploid ES cells with genetic modifications. The phenotypic analyses of derived mice support the genetic conflict theory of genomic imprinting. Taken together, our results highlight the factors necessary for crossing uniparental reproduction barriers in mammals.

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Project description:Haploid mammalian embryonic stem cells (ESCs) hold great promise for functional genetic studies and assisted reproduction. Recently, rodent androgenetic haploid ESCs (AG-haESCs) were generated from androgenetic blastocysts and functioned like sperm to produce viable offspring via the intracytoplasmic AG-haESCs injection into oocytes. However, the efficiency of this reproduction was very low. Most pups were growth-retarded and died shortly after birth, which is not practical for producing knockout animals. Further investigation suggested a possible link between the low birthrate and aberrant expression of imprinted genes. Here, we report the high-frequency generation of healthy, fertile mice from H19-Igf2 imprinting-locus modified AG-haESCs, which maintained normal paternal imprinting and pluripotency. Moreover, it is feasible to perform further genetic manipulations in these AG-haESCs. Our study provides a reliable and efficient tool to rapidly produce gene-modified mouse models and will benefit reproductive medicine in the future.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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