In vitro endoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture
In vitro endoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture
复制标题
在没有胚外组织和胚胎结构的情况下体外内胚层的出现和自组织
DOI：
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
M. Lutolf
中科院分区：
文献类型：
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作者：
S. Vianello;M. Lutolf
内胚层是在胚胎中产生呼吸和胃肠道系统器官的细胞谱系。独特的是，内胚层组织不仅来源于胚胎本身的后代（外胚层），而是由它们逐渐并入胚外基质（内脏内胚层）而产生。鉴于早期胚胎的配置，这样的范例需要外胚层内胚层祖细胞谈判胚胎隔室非常多样化的上皮特征，一个发展的偶然性反映了这样的事实，即关键的早期内胚层标记物，如Foxa 2和Sox 17已被一致发现嵌入在上皮形成所涉及的基因程序。为了探索胚胎内胚层前体的潜在细胞生物学，并探索内胚层发育、上皮身份和胚外混合之间的关系，我们利用了早期发育的体外模型Gastruloids。这些小鼠胚胎干细胞的自组织三维聚集体不具有胚外成分，也不显示典型的组织结构。然而，它们产生表达内胚层标志物的细胞。通过在整个体外发育过程中跟踪这些细胞，我们强调了上皮和内胚层身份之间持续和不间断的配对，FoxA 2 +/Sox 17+内胚层祖细胞从未通过间充质中间体过渡，也从未离开它们出现的上皮隔室。我们还记录了这些祖细胞戏剧性的形态发生，形成一个宏观的上皮原基，沿着整个前-后轴的Gastruloid。最后，我们发现，这个原基正确的模式到广泛的基因表达领域，和成熟的细胞与前前肠，中肠，后肠的身份在7天内的文化。因此，我们假设Gastruloids可能作为一个潜在的来源，内胚层类型难以获得通过经典的二维分化协议。
The endoderm is the cell lineage which gives rise in the embryo to the organs of the respiratory and gastrointestinal system. Uniquely, endodermal tissue does not just derive from descendants of the embryo proper (the epiblast) but instead arises from their gradual incorporation into an extraembryonic substrate (the visceral endoderm). Given the configuration of the early embryo, such a paradigm requires epiblast endodermal progenitors to negotiate embryonic compartments with very diverse epithelial character, a developmental contingency reflected by the fact that key early endodermal markers such as Foxa2 and Sox17 have been consistently found to be embedded within gene programmes involved in epithelialisation. To explore the underlying cell biology of embryonic endoderm precursors, and to explore the relationship between endoderm development, epithelial identity, and extraembryonic mixing, we leveraged Gastruloids, in vitro models of early development. These self-organising three-dimensional aggregates of mouse embryonic stem cells do not possess an extraembryonic component, nor do they appear to display typical tissue architecture. Yet, they generate cells expressing endodermal markers. By tracking these cells throughout in vitro development, we highlight a persistent and uninterrupted pairing between epithelial and endodermal identity, with FoxA2+/Sox17+ endoderm progenitors never transitioning through mesenchymal intermediates and never leaving the epithelial compartment in which they arise. We also document the dramatic morphogenesis of these progenitors into a macroscopic epithelial primordium extending along the entire anterior-posterior axis of the Gastruloid. Finally, we find that this primordium correctly patterns into broad domains of gene expression, and matures cells with anterior foregut, midgut, and hindgut identities within 7 days of culture. We thus postulate that Gastruloids may serve as a potential source of endodermal types difficult to obtain through classical 2D differentiation protocols.
影响因子：
2.7
作者：
Peter, Isabelle S.;Davidson, Eric H.
通讯作者：
Davidson, Eric H.
影响因子：
4
作者：
Pfendler, KC;Catuar, CS;Pedersen, RA
通讯作者：
Pedersen, RA
影响因子：
11.8
作者：
Kwon, Gloria S.;Viotti, Manuel;Hadjantonakis, Anna-Katerina
通讯作者：
Hadjantonakis, Anna-Katerina