Haploidy in somatic cells is induced by mature oocytes in mice

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.

Haploidy of somatic cells in mouse oocyte using somatic cell nuclear transfer

“…G0/G1 somatic cells, transferred into enucleated MII oocytes, could form a meiotic spindle-chromosomal complex in SCNT oocytes (Lee et al, 2022). A comparable spindle-chromosomal complex to that in intact metaphase oocytes was observed at 2 hours after SCNT.…”

“…Reconstructed oocytes were fertilized and then a set of somatic chromosomes was extruded from the cytoplasm to the form of a pseudo-polar body (PPB) (Lee et al, 2022). The remaining somatic and the sperm chromo-somes form two nuclei (2PNs) in the zygote.…”

“…Recently, one study tried somatic haploidization using somatic cell nuclear transfer with fertilization in mice (Lee et al, 2022). This study demonstrated that the somatic homologous chromosomes were segregated and the somatic haploid (SH)-embryos developed into blastocysts carrying somatic genomes.…”

Artificial Oocyte: Development and Potential Application

“…Recently, the present study revisited the haploidization of diploid somatic chromosomes using the somatic cell nuclear transfer (SCNT) [ 145 ]. Through it, it was confirmed that meiotic spindles were formed after the transfer of G0/G1 somatic cells into enucleated MII oocytes and succeeded to generate the somatic haploid chromosome ( Figure 7 ).…”

“…The embryo with the somatic haploid can then develop and produce live offspring. SCNT: somatic cell nuclear transfer [ 145 ].…”