Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR, USA.
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022 Anhui, China.
Sci Adv. 2024 Mar 8;10(10):eadk9001. doi: 10.1126/sciadv.adk9001.
Canonical mitotic and meiotic cell divisions commence with replicated chromosomes consisting of two sister chromatids. Here, we developed and explored a model of premature cell division, where nonreplicated, G/G-stage somatic cell nuclei are transplanted to the metaphase cytoplasm of mouse oocytes. Subsequent cell division generates daughter cells with reduced ploidy. Unexpectedly, genome sequencing analysis revealed proper segregation of homologous chromosomes, resulting in complete haploid genomes. We observed a high occurrence of somatic genome haploidization in nuclei from inbred genetic backgrounds but not in hybrids, emphasizing the importance of sequence homology between homologs. These findings suggest that premature cell division relies on mechanisms similar to meiosis I, where genome haploidization is facilitated by homologous chromosome interactions, recognition, and pairing. Unlike meiosis, no evidence of recombination between somatic cell homologs was detected. Our study offers an alternative in vitro gametogenesis approach by directly reprogramming diploid somatic cells into haploid oocytes.
有丝分裂和减数分裂的典型细胞分裂起始于由两条姐妹染色单体组成的复制染色体。在这里，我们开发并探索了一种过早细胞分裂的模型，其中非复制的 G/G 期体细胞核被移植到小鼠卵母细胞的中期细胞质中。随后的细胞分裂产生了具有较低倍性的子细胞。出乎意料的是，基因组测序分析显示同源染色体的正确分离，导致完整的单倍体基因组。我们观察到来自近交遗传背景的核中体细胞基因组单倍体化的高发生率，但在杂种中没有，这强调了同源之间序列同源性的重要性。这些发现表明，过早的细胞分裂依赖于类似于减数分裂 I 的机制，其中通过同源染色体的相互作用、识别和配对来促进基因组单倍体化。与减数分裂不同，没有检测到体细胞同源之间重组的证据。我们的研究提供了一种通过直接重编程二倍体体细胞为单倍体卵母细胞来进行体外配子发生的替代方法。
