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Re-evaluation of the causes of variation among mouse aggregation chimaeras

机译：重新评估小鼠聚集嵌合体之间变异的原因

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The composition of adult mouse aggregation chimaeras is much more variable than X-inactivation mosaics. An early theoretical model proposed that almost all the extra variation in chimaeras arises, before X-inactivation occurs, by spatially constrained, geometrical allocation of inner cell mass (ICM) cells to the epiblast and primitive endoderm (PrE). However, this is inconsistent with more recent embryological evidence. Analysis of published results for chimaeric blastocysts and mid-gestation chimaeras suggested that some variation exists among chimaeric morulae and more variation arises both when morula cells are allocated to the ICM versus the trophectoderm (TE) and when ICM cells are allocated to the epiblast versus the PrE. Computer simulation results were also consistent with the conclusion that stochastic allocation of cells to blastocyst lineages in two steps, without the type of geometrical sampling that was originally proposed, could cause a wide variation in chimaeric epiblast composition. Later allocation events will cause additional variation among both chimaeras and X-inactivation mosaics. We also suggest that previously published U-shaped frequency distributions for chimaeric placenta composition might be explained by how TE cells are allocated to the polar TE and/or the subsequent movement of cells from polar TE to mural TE.
机译：成年小鼠聚集嵌合体的组成比X灭活镶嵌体可变得多。早期的理论模型提出，在X灭活发生之前，通过将内部细胞团（ICM）细胞的几何空间分配给上皮细胞和原始内胚层（PrE），在嵌合体中几乎所有额外的变化都会出现。但是，这与最近的胚胎学证据不一致。对已发表的关于嵌合体胚泡和妊娠中期嵌合体的结果的分析表明，在嵌合体桑among之间存在一些变异，当将桑cells细胞分配给ICM与滋养外胚层（TE）以及将ICM细胞分配给上胚层与胚泡时，会出现更多的变异。 PrE。计算机仿真结果也与以下结论一致：如果不按照最初提出的那样进行几何采样，则在两个步骤中将细胞随机分配到囊胚谱系中可能会导致Chimaeric Epiblast组成差异很大。以后的分配事件将导致嵌合体和X灭活镶嵌之间的额外变化。我们还建议，先前发布的用于嵌合胎盘的U形频率分布可以通过TE细胞如何分配给极性TE和/或随后细胞从极性TE迁移到壁厚TE来解释。

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