Developmental potential and behavior of tetraploid cells in the mouse embryo

Developmental potential and behavior of tetraploid cells in the mouse embryo
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DOI:
10.1016/j.ydbio.2005.09.028
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发表时间:
2005-12-01
影响因子:
2.7
通讯作者:
Behringer, RR
Behringer, RR
中科院分区:
生物学3区
文献类型:
--
作者:
Eakin, GS;Hadjantonakis, AK;Behringer, RR

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四倍体(4n)小鼠胚胎在不同的发育阶段死亡。通过研究F2杂交和远交种小鼠的4n胚胎,我们发现4n发育潜力受到遗传背景的影响。胚胎外组织中X染色体连接的eGFP转基因的印迹失活在4n个胚胎中正确发生。使用组蛋白H2b:eGFP报告基因实时成像显示,与二倍体(2n)胚胎相比,4n植入前胚胎的卵裂率降低。以前已经知道,二倍体(2n)胚胎与胚胎干(ES)细胞结合产生的小鼠嵌合体会在外胚层来源的组织中产生两种成分的混合物。相比之下,使用带有胚胎干细胞的4n宿主胚胎限制了嵌合体胚胎区域的4n细胞,导致小鼠被认为完全来自胚胎干细胞。利用H2b:eGFP转基因小鼠和ES细胞,在单细胞分辨率下测定4n细胞在4n:2n注射和聚集嵌合体中的行为。我们发现在分析的每个嵌合体中,在原肠胚形成时胚胎外胚层都有4n个细胞的显著贡献。我们发现胚胎区域在原肠胚形成后从嵌合组织转变为2n组织,四倍体细胞可以持续到妊娠中期。这些发现表明,先前发表的四倍体互补试验的结果可能受到四倍体细胞在其他二倍体胚胎区域存在的影响。(C) 2005爱思唯尔公司版权所有。
Tetraploid (4n) mouse embryos die at variable developmental stages. By examining 4n embryos from F2 hybrid and outbred mice, we show that 4n developmental potential is influenced by genetic background. The imprinted inactivation of an X chromosome-linked eGFP transgene in extraembryonic tissues occurred correctly in 4n embryos. A decrease of the cleavage rate in 4n preimplantation embryos compared to diploid (2n) embryos was revealed by real-time imaging, using a histone H2b:eGFP reporter. It has previously been known that mouse chimeras produced by the combination of diploid (2n) embryos with embryonic stem (ES) cells result in mixtures of the two components in epiblast-derived tissues. In contrast, the use of 4n host embryos with ES cells restricts 4n cells from the embryonic regions of chimeras, resulting in mice that are believed to be completely ES-derived. Using H2b:eGFP transgenic mice and ES cells, the behavior of 4n cells was determined at single cell resolution in 4n:2n injection and aggregation chimeras. We found a significant contribution of 4n cells to the embryonic ectoderm at gastrulation in every chimera analyzed. We show that the transition of the embryonic regions from a chimeric tissue to a predominantly 2n tissue occurs after gastrulation and that tetraploid cells may persist to midgestation. These findings suggest that the results of previously published tetraploid complementation assays may be influenced by the presence of tetraploid cells in the otherwise diploid embryonic regions. (C) 2005 Elsevier Inc. All rights reserved.