Chromosome territory reorganization through artificial chromosome fusion is negligible to cell fate determination and mouse development

Abstract

SummaryChromosomes occupy discrete spaces in the interphase cell nucleus, called chromosome territory. The structural and functional relevance of chromosome territory remains elusive. We fused chromosome 15 and 17 in mouse haploid embryonic stem cells (haESCs), resulting in distinct changes of territories in the corresponding native chromosomes, but affecting little on gene expression, pluripotency and gamete functions of haESCs. The karyotype engineered haESCs were successfully implemented in cultivating heterozygous (2n=39) and homozygous (2n=38) mouse models. The mice containing fusion-chromosome are fertile, and their representative tissues and organs display no phenotypic abnormalities, suggesting mouse development unscathed. These results indicate that the mammalian chromosome architectures are highly resilient, and reorganization of chromosome territories can be readily tolerated during cell differentiation and mouse development.