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

胚胎发育过程中早期发育的研究对于提高基础生物学和临床重要性至关重要。然而，由于伦理界限和无法在子宫内获得植入的胚胎，它是有限的。因此，使用多能干细胞开发一种名为原肠突的合成胚胎模型的需求越来越大。三维原肠突可以重现原肠胚期胚胎的一些基本方面，包括原肠形成后、破坏对称性和沿前后轴极化。然而，原肠模型缺乏胚外组织(EXT)，不能很好地捕捉早期神经器官发生。因此，我们的目标是通过将人诱导的多能干细胞(HiPSCs)与水凝胶冷冻剂相结合来改进胃液培养。由于较软的冷冻凝胶(0.5%琼脂糖凝胶)显示出显著的促进HiPSCs分化为3D生理相关器官模型胚胎发生的希望，CyroGel的刚性可以促进细胞反应。这些结构显示了神经中胚层前体细胞在整个体轴延伸过程中的时空受限模式。我们发现SOX2和T-BRA的拮抗活性提示神经和中胚层命运的指定。总而言之，这项研究可能预见到，神经中胚层模式定义了两条不同的途径，它们构成了体节和神经管。

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.