Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells.
Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells.
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DOI：
10.1002/advs.202203614
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发表时间：
2023-02
期刊：
影响因子：
15.1
通讯作者：
Kilian, Kristopher
中科院分区：
文献类型：
--
作者：
Srivastava, Pallavi;Romanazzo, Sara;Kopecky, Chantal;Nemec, Stephanie;Ireland, Jake;Molley, Thomas G.;Lin, Kang;Jayathilaka, Pavithra B.;Pandzic, Elvis;Yeola, Avani;Chandrakanthan, Vashe;Pimanda, John;Kilian, Kristopher
原肠胚形成是胚胎发育的一个阶段，其中三个胚层的出现决定了人体的计划。原肠胚形成的体外模型已通过用可溶性形态发生素处理多能干细胞来触发分化得到证实。然而，体内原肠胚形成是一个通过可溶性梯度和生物物理力之间的反馈协调的多阶段过程，多能外胚层转变为原条，随后进行胚层分离。在这里，作者展示了如何将多能干细胞限制在水凝胶岛上，从而触发形态发生，从而反映体内原肠胚形成之前的阶段，而无需外源补充剂。初始接种后数小时内，细胞在边界处表现出收缩表型，从而导致增殖增强、yes相关蛋白（YAP）易位、上皮细胞向间质细胞转变以及SRY盒转录因子17（SOX17）+ T/BRACHYURY+细胞的出现。分子谱和通路分析揭示了机械转导耦合无翼型（WNT）信号在协调分化中的作用，这与整个有机体发育模型中观察到的过程相似。两天后，菌落形成多层聚集体，可以将其移除以进一步生长和分化。这种方法展示了材料如何单独启动原肠胚形成，从而提供体外发育模型和支持类器官生物工程工作的工具。将多能干细胞限制在水凝胶岛中，可以启动上皮细胞向间充质细胞的转变，并形成原始条纹状细胞群，而无需添加可溶性触发器。材料引导的形态发生是机械转导和无翼型（WNT）信号传导的结果，与体内原肠胚形成模型相似。
Gastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes‐associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY‐box transcription factor 17 (SOX17)+ T/BRACHYURY+ cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction‐coupled wingless‐type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts. Confining pluripotent stem cells to hydrogel islands initiates epithelial to mesenchymal transition and formation of a primitive streak‐like population, without the addition of soluble triggers. The materials directed morphogenesis is a result of mechanotransduction and wingless type (WNT) signaling, which bears similarities to in vivo models of gastrulation.
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影响因子：
30.8
作者：
Liu, PT;Wakamiya, M;Bradley, A
通讯作者：
Bradley, A
影响因子：
16.6
作者：
Lin, Yongshun;Li, Xiao-Yan;Willis, Amanda L.;Liu, Chengyu;Chen, Guokai;Weiss, Stephen J.
通讯作者：
Weiss, Stephen J.
DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan
影响因子：
4.6
作者：
Lim, Jormay;Thiery, Jean Paul
通讯作者：
Thiery, Jean Paul
影响因子：
4.6
作者：
Cha, Sang-Wook;Tadjuidje, Emmanuel;Heasman, Janet
通讯作者：
Heasman, Janet