研究人员报告了小鼠的染色体程序化连接，这导致在实验室中创造了新的核型。利用单倍体胚胎干细胞和基因编辑，研究人员融合了小鼠两条最大的染色体，即1号和2号染色体，以及两条中等大小的染色体，即4号和5号染色体。染色质构象和干细胞分化受到的影响很小。然而，携带融合的1号和2号染色体的核型导致有丝分裂停止、多倍体化和胚胎死亡，而由4号和5号染色体组成的较小的融合染色体却能传给同源的后代。这些结果表明，在哺乳动物中进行染色体水平的工程化是可行的。
据悉，染色体工程在酵母中已被成功尝试，但在包括哺乳动物在内的高等真核生物中仍然具有挑战性。
附：英文原文
Title: A sustainable mouse karyotype created by programmed chromosome fusion
Author: Li-Bin Wang, Zhi-Kun Li, Le-Yun Wang, Kai Xu, Tian-Tian Ji, Yi-Huan Mao, Si-Nan Ma, Tao Liu, Cheng-Fang Tu, Qian Zhao, Xu-Ning Fan, Chao Liu, Li-Ying Wang, You-Jia Shu, Ning Yang, Qi Zhou, Wei Li
Issue&Volume: 2022-08-26
Abstract: 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.
DOI: abm1964
Source: https://www.science.org/doi/10.1126/science.abm1964