Developmental bias in cleavage-stage mouse blastomeres.
Developmental bias in cleavage-stage mouse blastomeres.
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DOI：
10.1016/j.cub.2012.10.054
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发表时间：
2013-01-07
期刊：
影响因子：
9.2
通讯作者：
Eggan, Kevin
中科院分区：
文献类型：
--
作者：
Tabansky, Inna;Lenarcic, Alan;Draft, Ryan W.;Loulier, Karine;Keskin, Derin B.;Rosains, Jacqueline;Rivera-Feliciano, Jose;Lichtman, Jeff W.;Livet, Jean;Stern, Joel N. H.;Sanes, Joshua R.;Eggan, Kevin
卵裂期小鼠胚胎由表面相当的卵裂球组成，这些卵裂球将产生胚胎内细胞团（ICM）和支持性滋养外胚层（TE）。然而，每个卵裂球对这两个谱系的贡献是否可以通过偶然来解释仍然没有定论。解决卵裂球细胞命运的问题可能具有实际意义，因为植入前遗传学诊断（PGD）需要从早期人类胚胎中取出卵裂球。为了确定卵裂球分配到两个最早的谱系是否是随机的，我们开发并利用了重组介导的非侵入性组合荧光标记方法进行胚胎谱系追踪。当我们在卵裂阶段诱导重组时，我们观察到所得标记克隆对滋养外胚层或胚胎亚组中的内细胞团的贡献存在统计学显著偏倚。令人惊讶的是，我们没有发现克隆在胚胎和非胚半球的晚期囊胚和它们的分配TE和ICM的本地化之间的相关性，这表明TE-ICM的偏见分别从胚胎-非胚偏见。Rainbow谱系追踪还使我们能够证明在胚泡中观察到的偏差持续到植入后阶段，因此与后续发育相关。我们在这里描述的彩虹转基因小鼠使我们能够检测早期发育中的谱系依赖性偏倚。它们还应该能够评估哺乳动物祖细胞在各种组织中的发育等效性。
The cleavage stage mouse embryo is composed of superficially equivalent blastomeres that will generate both the embryonic inner cell mass (ICM) and the supportive trophectoderm (TE). However, it remains unsettled whether the contribution of each blastomere to these two lineages can be accounted for by chance. Addressing the question of blastomere cell fate may be of practical importance, as preimplantation genetic diagnosis (PGD) requires removal of blastomeres from the early human embryo. To determine if blastomere allocation to the two earliest lineages is random, we developed and utilized a recombination-mediated, non-invasive combinatorial fluorescent labeling method for embryonic lineage tracing. When we induced recombination at cleavage stages, we observed a statistically significant bias in the contribution of the resulting labeled clones to the trophectoderm or the inner cell mass in a subset of embryos. Surprisingly, we did not find a correlation between localization of clones in the embryonic and abembryonic hemispheres of the late blastocyst and their allocation to the TE and ICM, suggesting that TE-ICM bias arises separately from embryonic-abembryonic bias. Rainbow lineage tracing also allowed us to demonstrate that the bias observed in the blastocyst persists into post-implantation stages, and therefore has relevance for subsequent development. The Rainbow transgenic mice that we describe here have allowed us to detect lineage-dependent bias in early development. They should also enable assessment of the developmental equivalence of mammalian progenitor cells in a variety of tissues.
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