Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells
Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells
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DOI：
10.1016/j.cell.2015.11.035
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发表时间：
2016-01-14
期刊：
影响因子：
64.5
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Li, Xin;Cui, Xiao-Long;Zhou, Qi
哺乳动物种间杂种为物种形成、基因表达调控和X染色体失活（XCI）机制的研究提供了独特的优势，但受到其有限的自然资源的限制。以前人工产生的哺乳动物种间杂交细胞通常是四倍体，基因组不稳定，发育能力有限。在这里，我们报告的代小鼠异源二倍体胚胎干细胞（AdESCs）融合单倍体ESCs的两个物种。AdESCs具有稳定的异源二倍体基因组，并且能够分化成所有三个胚层和早期生殖细胞。小鼠和大鼠的等位基因对大多数基因的表达都有相当的贡献。我们已经证明AdESCs作为一个强大的工具来研究调节X染色体失活的机制，并确定X失活逃逸基因，以及有效地识别基因调节物种之间的表型差异。类似的方法也可以用来创造其他远亲物种的杂交AdESCs。
Mammalian interspecific hybrids provide unique advantages for mechanistic studies of speciation, gene expression regulation, and X chromosome inactivation (XCI) but are constrained by their limited natural resources. Previous artificially generated mammalian interspecific hybrid cells are usually tetraploids with unstable genomes and limited developmental abilities. Here, we report the generation of mouserat allodiploid embryonic stem cells (AdESCs) by fusing haploid ESCs of the two species. The AdESCs have a stable allodiploid genome and are capable of differentiating into all three germ layers and early-stage germ cells. Both the mouse and rat alleles have comparable contributions to the expression of most genes. We have proven AdESCs as a powerful tool to study the mechanisms regulating X chromosome inactivation and to identify X inactivation-escaping genes, as well as to efficiently identify genes regulating phenotypic differences between species. A similar method could be used to create hybrid AdESCs of other distantly related species.