论文题目：A sustainable mouse karyotype created by programmed chromosome fusion

作者: Wang LB, Li ZK, Wang LY, Xu K, Ji TT, Mao YH, Ma SN, Liu T, Tu CF, Zhao Q, Fan XN, Liu C, Wang LY, Shu YJ, Yang N, Zhou Q, Li W

日期：2022.8

发表期刊：Science

doi：10.1126/science.abm1964

摘要：

   Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring. Our results suggest the feasibility of chromosome-level engineering in mammals.