血管・尿排泄経路を有する次世代腎臓オルガノイドの作成

胚胎发生过程中早期发育的研究对于推进基础生物学和临床重要性至关重要。然而，由于伦理界限和子宫内植入胚胎的不可及性，它是有限的。因此，通过使用多能干细胞开发称为类胃体的合成胚胎模型的需求不断增加。三维（3D）gastroloids能够重演原肠胚阶段胚胎的一些基本方面，包括原肠胚形成后打破对称性和沿沿着前后轴极化。然而，胃类模型缺乏胚外组织（EXT），是不完善的捕捉早期神经器官发生。因此，我们的目标是通过将人类诱导的多能干细胞（hiPSC）与基于水凝胶的冷冻凝胶连接来改善胃样细胞培养。冷冻凝胶的硬度可以促进细胞反应，因为较软的冷冻凝胶（0.5%琼脂糖）显示出促进hiPSC分化为胚胎发生的3D生理相关类器官模型的显著前景。这些构建体显示神经中胚层祖细胞在整个体轴伸长过程中的时空限制模式。我们发现Sox 2和T-bra的拮抗活性表明神经和中胚层命运的规范。总的来说，这项研究可以设想，神经中胚层的图案定义了两个不同的路线，有助于体节和神经管的存在。

The study of early development during embryogenesis is crucial for advancing fundamental biological and clinical importance. Yet it is limited due to ethical boundaries and the inaccessibility of implanted embryos in utero. Hence, there is a rising demand for developing a synthetic embryonic model called gastruloids by using pluripotent stem cells. The three-dimensional (3D) gastruloids enable the recapitulation of some essential aspects of gastrula-stage embryos including post gastrulation break symmetry and polarized along an anteroposterior axis. However, gastruloid model lacks extraembryonic tissue (EXT) and is imperfect to capture early neural organogenesis. Thus, we aim to improve gastruloid cultureby interfacing human-induced pluripotent stem cells (hiPSCs) with hydrogel-based cryogel. The stiffness of cyrogel can promote cellular response, as softer cryogel (0.5% agarose) showed significant promise to facilitate hiPSCs differentiation on to 3D physiologically relevant organoid model of embryogenesis. These constructs display spatiotemporally confined patterning of neuromesodermal progenitors throughout body axis elongation. We found antagonistic activities of Sox2 and T-bra suggest the specification of neural and mesodermal fates. Collectively, this study may envision that the neuromesodermal patterning define the existence of two distinct routes that contribute to the somites and neural tube.