Branching development of early post-implantation human embryonic-like tissues in 3D stem cell culture.
Branching development of early post-implantation human embryonic-like tissues in 3D stem cell culture.
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DOI：
10.1016/j.biomaterials.2021.120898
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发表时间：
2021-08
期刊：
影响因子：
14
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Chen K;Zheng Y;Xue X;Liu Y;Resto Irizarry AM;Tang H;Fu J
人类胚胎干细胞（human embryonic stem cells，hESCs）具有自组织和产生图案化组织的内在能力。通过调节物理环境和用化学信号引发诱导hESC形成胚胎样结构的体外模型已成为解剖早期人类发育的调控机制的有力工具。在这里，我们提出了一个三维悬浮培养系统的hESC，可以产生植入后，前原肠胚形成胚胎样组织在一个有效的和可控的方式。在3D悬浮培养中，模拟着床后、原肠胚形成前羊膜囊的不对称组织的发育效率约为50%。定量成像分析和无监督轨迹分析显示，hESC聚集体首先进入表达Brachyury（或T）的过渡阶段，然后它们的发育分支成不同的路径，分别发育成不对称的胚胎样组织、胚胎样组织和中胚层样组织。此外，胚胎样结构的分支发育轨迹受到初始细胞接种密度或hESCs簇大小的影响。在较小的初始细胞接种密度下观察到较高百分比的类神经胶质组织。相反，大的初始细胞接种密度的hESC促进中胚层样组织的发育。中等细胞接种密度的hESC在三维悬浮培养中促进了不对称胚胎样组织的发育。我们的结果表明，hESCs具有感知初始细胞群体大小的内在能力，这反过来又调节它们的分化和自组织形成不同的胚胎样组织。因此，我们的3D悬浮培养提供了一个有前途的实验工具，研究组织拓扑结构和自组织之间的相互作用，并使用体外hESC为基础的模型进行胚胎发育。
Human embryonic stem cells (hESCs) have the intrinsic capacity to self-organize and generate patterned tissues. In vitro models that coax hESCs to form embryonic-like structures by modulating physical environments and priming with chemical signals have become a powerful tool for dissecting the regulatory mechanisms underlying early human development. Here we present a 3D suspension culture system of hESCs that can generate post-implantation, pre-gastrulation embryonic-like tissues in an efficient and controllable manner. The efficiency of the development of asymmetric tissues, which mimic the post-implantation, pre-gastrulation amniotic sac, was about 50% in the 3D suspension culture. Quantitative imaging profiling and unsupervised trajectory analysis revealed that hESC aggregates first entered into a transitional stage expressing Brachyury (or T), before their development branched into different paths to develop into asymmetric embryonic-like tissues, amniotic-like tissues, and mesodermal-like tissues, respectively. Moreover, the branching developmental trajectory of embryonic-like structures was affected by the initial cell seeding density or cluster size of hESCs. A higher percentage of amniotic-like tissues was observed under a small initial cell seeding density of hESCs. Conversely, a large initial cell seeding density of hESCs promoted the development of mesodermal-like tissues. Intermediate cell seeding densities of hESCs in the 3D suspension culture promoted the development of asymmetric embryonic-like tissues. Our results suggest that hESCs have the intrinsic capability to sense the initial cell population size, which in turn regulates their differentiation and self-organization into different embryonic-like tissues. Our 3D suspension culture thus provides a promising experimental tool to study the interplay between tissue topology and self-organization and progressive embryonic development using in vitro hESC-based models.
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影响因子：
46.9
作者：
Setty M;Tadmor MD;Reich-Zeliger S;Angel O;Salame TM;Kathail P;Choi K;Bendall S;Friedman N;Pe'er D
通讯作者：
Pe'er D
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
5.3
作者：
Carver, EA;Jiang, RL;Gridley, T
通讯作者：
Gridley, T
影响因子：
4.6
作者：
Niakan, Kathy K.;Han, Jinnuo;Pera, Renee A. Reijo
通讯作者：
Pera, Renee A. Reijo
影响因子：
64.8
作者：
Nakamura, Tomonori;Okamoto, Ikuhiro;Saitou, Mitinori
通讯作者：
Saitou, Mitinori