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

Commun Biol. 2022 Jan 25;5(1):95. doi: 10.1038/s42003-022-03040-5.

Authors

Yeonmi Lee^#^{1

2}, Aysha Trout^#³, Nuria Marti-Gutierrez^#⁴, Seoon Kang^{1

5}, Philip Xie³, Aleksei Mikhalchenko⁴, Bitnara Kim¹, Jiwan Choi^{1

5}, Seongjun So^{1

5}, Jongsuk Han¹, Jing Xu^{4

6

7}, Amy Koski⁴, Hong Ma⁴, Junchul David Yoon⁴, Crystal Van Dyken⁴, Hayley Darby⁴, Dan Liang⁴, Ying Li⁴, Rebecca Tippner-Hedges⁴, Fuhua Xu^{4

7}, Paula Amato^{4

7}, Gianpiero D Palermo⁸, Shoukhrat Mitalipov⁹, Eunju Kang^{10

11}

Affiliations

¹ Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi, 13488, South Korea.
² Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi, 13488, South Korea.
³ The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
⁴ Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland, OR, 97239, USA.
⁵ Department of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
⁶ Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR, 97006, USA.
⁷ Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, 97239, USA.
⁸ The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. [email protected].
⁹ Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland, OR, 97239, USA. [email protected].
¹⁰ Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi, 13488, South Korea. [email protected].
¹¹ Center for Embryo and Stem Cell Research, CHA Advanced Research Institute, CHA University, Seongnam, Gyeonggi, 13488, South Korea. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromosomes
Embryonic Development
Female
G1 Phase Cell Cycle Checkpoints
G2 Phase Cell Cycle Checkpoints
Haploidy
Male
Mice
Mice, Inbred Strains
Nuclear Transfer Techniques
Oocytes / physiology*
Spindle Apparatus

Abstract

Publication types

MeSH terms

Grants and funding