研究実績の概要 |
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 culture by 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.
|