Haploidy in somatic cells is induced by mature oocytes in mice

Yeonmi Lee; Aysha Trout; Nuria Marti-Gutierrez; Seoon Kang; Philip Xie; Aleksei Mikhalchenko; Bitnara Kim; Jiwan Choi; Seongjun So; Jongsuk Han; Jing Xu; Amy Koski; Hong Ma; Junchul David Yoon; Crystal Van Dyken; Hayley Darby; Dan Liang; Ying Li; Rebecca Tippner-Hedges; Fuhua Xu; Paula Amato; Gianpiero D. Palermo; Shoukhrat Mitalipov; Eunju Kang

doi:10.1038/s42003-022-03040-5

Haploidy in somatic cells is induced by mature oocytes in mice

Yeonmi Lee, Aysha Trout, Nuria Marti-Gutierrez, Seoon Kang, Philip Xie, Aleksei Mikhalchenko, Bitnara Kim, Jiwan Choi, Seongjun So, Jongsuk Han, Jing Xu, Amy Koski, Hong Ma, Junchul David Yoon, Crystal Van Dyken, Hayley Darby, Dan Liang, Ying Li, Rebecca Tippner-Hedges, Fuhua XuPaula Amato, Gianpiero D. Palermo, Shoukhrat Mitalipov, Eunju Kang

Obstetrics and Gynecology

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Abstract

Haploidy is naturally observed in gametes; however, attempts of experimentally inducing haploidy in somatic cells have not been successful. Here, we demonstrate that the replacement of meiotic spindles in mature metaphases II (MII) arrested oocytes with nuclei of somatic cells in the G0/G1 stage of cell cycle results in the formation of de novo spindles consisting of somatic homologous chromosomes comprising of single chromatids. Fertilization of such oocytes with sperm triggers the extrusion of one set of homologous chromosomes into the pseudo-polar body (PPB), resulting in a zygote with haploid somatic and sperm pronuclei (PN). Upon culture, 18% of somatic-sperm zygotes reach the blastocyst stage, and 16% of them possess heterozygous diploid genomes consisting of somatic haploid and sperm homologs across all chromosomes. We also generate embryonic stem cells and live offspring from somatic-sperm embryos. Our finding may offer an alternative strategy for generating oocytes carrying somatic genomes.

Original language	English (US)
Article number	95
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03040-5
State	Published - Dec 2022

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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10.1038/s42003-022-03040-5

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Lee, Y., Trout, A., Marti-Gutierrez, N., Kang, S., Xie, P., Mikhalchenko, A., Kim, B., Choi, J., So, S., Han, J., Xu, J., Koski, A., Ma, H., Yoon, J. D., Van Dyken, C., Darby, H., Liang, D., Li, Y., Tippner-Hedges, R., ... Kang, E. (2022). Haploidy in somatic cells is induced by mature oocytes in mice. Communications Biology, 5(1), Article 95. https://doi.org/10.1038/s42003-022-03040-5

Lee, Y, Trout, A, Marti-Gutierrez, N, Kang, S, Xie, P, Mikhalchenko, A, Kim, B, Choi, J, So, S, Han, J, Xu, J, Koski, A, Ma, H, Yoon, JD, Van Dyken, C, Darby, H, Liang, D, Li, Y, Tippner-Hedges, R, Xu, F, Amato, P, Palermo, GD, Mitalipov, S & Kang, E 2022, 'Haploidy in somatic cells is induced by mature oocytes in mice', Communications Biology, vol. 5, no. 1, 95. https://doi.org/10.1038/s42003-022-03040-5

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abstract = "Haploidy is naturally observed in gametes; however, attempts of experimentally inducing haploidy in somatic cells have not been successful. Here, we demonstrate that the replacement of meiotic spindles in mature metaphases II (MII) arrested oocytes with nuclei of somatic cells in the G0/G1 stage of cell cycle results in the formation of de novo spindles consisting of somatic homologous chromosomes comprising of single chromatids. Fertilization of such oocytes with sperm triggers the extrusion of one set of homologous chromosomes into the pseudo-polar body (PPB), resulting in a zygote with haploid somatic and sperm pronuclei (PN). Upon culture, 18% of somatic-sperm zygotes reach the blastocyst stage, and 16% of them possess heterozygous diploid genomes consisting of somatic haploid and sperm homologs across all chromosomes. We also generate embryonic stem cells and live offspring from somatic-sperm embryos. Our finding may offer an alternative strategy for generating oocytes carrying somatic genomes.",

author = "Yeonmi Lee and Aysha Trout and Nuria Marti-Gutierrez and Seoon Kang and Philip Xie and Aleksei Mikhalchenko and Bitnara Kim and Jiwan Choi and Seongjun So and Jongsuk Han and Jing Xu and Amy Koski and Hong Ma and Yoon, {Junchul David} and {Van Dyken}, Crystal and Hayley Darby and Dan Liang and Ying Li and Rebecca Tippner-Hedges and Fuhua Xu and Paula Amato and Palermo, {Gianpiero D.} and Shoukhrat Mitalipov and Eunju Kang",

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AU - Lee, Yeonmi

AU - Trout, Aysha

AU - Marti-Gutierrez, Nuria

AU - Kang, Seoon

AU - Xie, Philip

AU - Mikhalchenko, Aleksei

AU - Kim, Bitnara

AU - Choi, Jiwan

AU - So, Seongjun

AU - Han, Jongsuk

AU - Xu, Jing

AU - Koski, Amy

AU - Ma, Hong

AU - Yoon, Junchul David

AU - Van Dyken, Crystal

AU - Darby, Hayley

AU - Liang, Dan

AU - Li, Ying

AU - Tippner-Hedges, Rebecca

AU - Xu, Fuhua

AU - Amato, Paula

AU - Palermo, Gianpiero D.

AU - Mitalipov, Shoukhrat

AU - Kang, Eunju

PY - 2022/12

Y1 - 2022/12

N2 - Haploidy is naturally observed in gametes; however, attempts of experimentally inducing haploidy in somatic cells have not been successful. Here, we demonstrate that the replacement of meiotic spindles in mature metaphases II (MII) arrested oocytes with nuclei of somatic cells in the G0/G1 stage of cell cycle results in the formation of de novo spindles consisting of somatic homologous chromosomes comprising of single chromatids. Fertilization of such oocytes with sperm triggers the extrusion of one set of homologous chromosomes into the pseudo-polar body (PPB), resulting in a zygote with haploid somatic and sperm pronuclei (PN). Upon culture, 18% of somatic-sperm zygotes reach the blastocyst stage, and 16% of them possess heterozygous diploid genomes consisting of somatic haploid and sperm homologs across all chromosomes. We also generate embryonic stem cells and live offspring from somatic-sperm embryos. Our finding may offer an alternative strategy for generating oocytes carrying somatic genomes.

AB - Haploidy is naturally observed in gametes; however, attempts of experimentally inducing haploidy in somatic cells have not been successful. Here, we demonstrate that the replacement of meiotic spindles in mature metaphases II (MII) arrested oocytes with nuclei of somatic cells in the G0/G1 stage of cell cycle results in the formation of de novo spindles consisting of somatic homologous chromosomes comprising of single chromatids. Fertilization of such oocytes with sperm triggers the extrusion of one set of homologous chromosomes into the pseudo-polar body (PPB), resulting in a zygote with haploid somatic and sperm pronuclei (PN). Upon culture, 18% of somatic-sperm zygotes reach the blastocyst stage, and 16% of them possess heterozygous diploid genomes consisting of somatic haploid and sperm homologs across all chromosomes. We also generate embryonic stem cells and live offspring from somatic-sperm embryos. Our finding may offer an alternative strategy for generating oocytes carrying somatic genomes.

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Haploidy in somatic cells is induced by mature oocytes in mice

Abstract

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