Trophectoderm regeneration to support full-term development in the inner cell mass isolated from bovine blastocyst
Trophectoderm regeneration to support full-term development in the inner cell mass isolated from bovine blastocyst
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DOI：
10.1074/jbc.ra119.010746
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发表时间：
2019-12-13
影响因子：
4.8
通讯作者：
Kawahara, Manabu
中科院分区：
文献类型：
--
作者：
Kohri, Nanami;Akizawa, Hiroki;Kawahara, Manabu
哪一个先出现：组织结构还是细胞分化？虽然不同的细胞类型建立了描绘胚胎内部和外部的不同结构，但它们逐渐由胚泡阶段指定，此时形成两种类型的细胞谱系：内细胞团（ICM）和滋养外胚层（TE）。这种内-外方面可以通过实验从囊胚中分离ICM来转换，导致构成ICM最外层的卵裂球的后验外化。在这里，我们研究了分离的小鼠和牛ICM的全能性，以确定它们是否有能力进行TE再生。令人惊讶的是，从具有重新形成的囊胚腔的牛分离的ICM（re-iICM）产生小牛，但没有小鼠re-iICM发育到足月。为了进一步探索小鼠和牛re-iICM之间发育能力差异的原因，我们研究了原始内胚层的代表性分子标记物SOX 17蛋白表达。SOX 17在小鼠和牛胚胎中的定位模式完全不同。特别地，TE中的异位SOX 17定位可能与小鼠re-iICM的致死性相关。与此同时，转录组测序显示，一些牛re-iICM显示出与完整囊胚相似的TE特异性基因转录模式。我们的研究结果表明，TE再生能力保持在牛ICMs比小鼠ICMs更长的时间，并提供证据表明，ICM/TE细胞命运的决定是由结构决定因素，包括在哺乳动物胚胎中的每个卵裂球的位置信息的影响。
Which comes first: tissue structure or cell differentiation? While different cell types establish distinct structures delineating the in- and outside of an embryo, they progressively become specified by the blastocyst stage, when two types of cell lineages are formed: inner cell mass (ICM) and trophectoderm (TE). This inside-outside aspect can be experimentally converted by the isolation of the ICM from a blastocyst, leading to a posteriori externalization of the blastomeres composing the outermost layer of the ICM. Here, we investigated the totipotency of isolated mouse and bovine ICMs to determine whether they are competent for TE regeneration. Surprisingly, a calf was generated from the bovine isolated ICM with re-formed blastocoel (re-iICM), but no mouse re-iICMs developed to term. To further explore the cause of difference in developmental competency between the mouse and bovine re-iICMs, we investigated the SOX17 protein expression that is a representative molecular marker of primitive endoderm. The localization pattern of SOX17 was totally different between mouse and bovine embryos. Particularly, the ectopic SOX17 localization in the TE might be associated with lethality of mouse re-iICMs. Meanwhile, transcriptome sequencing revealed that some of the bovine re-iICMs showed transcriptional patterns of TE-specific genes similar to those of whole blastocysts. Our findings suggest that TE regeneration competency is maintained longer in bovine ICMs than in mouse ICMs and provide evidence that the ICM/TE cell fate decision is influenced by structural determinants, including positional information of each blastomere in mammalian embryos.