Yang Yang, Laterza Cecilia, Stuart Hannah T, Michielin Federica, Gagliano Onelia, Urciuolo Anna, Elvassore Nicola
Department of Industrial Engineering (DII), University of Padova, Padova, Italy.
Fondazione Ricerca Biomedica Avanzata Onlus, Veneto Institute of Molecular Medicine, Padova, Italy.
Front Bioeng Biotechnol. 2022 Jul 22;10:907159. doi: 10.3389/fbioe.2022.907159. eCollection 2022.
The human developmental processes during the early post-implantation stage instruct the specification and organization of the lineage progenitors into a body plan. These processes, which include patterning, cell sorting, and establishment of the three germ layers, have been classically studied in non-human model organisms and only recently, through micropatterning technology, in a human-specific context. Micropatterning technology has unveiled mechanisms during patterning and germ layer specification; however, cell sorting and their segregation in specific germ layer combinations have not been investigated yet in a human-specific system. Here, we developed an model of human ectodermal patterning, in which human pluripotent stem cells (hPSCs) self-organize to form a radially regionalized neural and non-central nervous system (CNS) ectoderm. We showed that by using micropatterning technology and by modulating BMP and WNT signals, we can regulate the appearance and spatial distribution of the different ectodermal populations. This pre-patterned ectoderm can be used to investigate the cell sorting behavior of hPSC-derived meso-endoderm cells, with an endoderm that segregates from the neural ectoderm. Thus, the combination of micro-technology with germ layer cross-mixing enables the study of cell sorting of different germ layers in a human context.
植入后早期阶段的人类发育过程指导谱系祖细胞的特化和组织，形成身体蓝图。这些过程，包括模式形成、细胞分选以及三个胚层的建立，传统上是在非人类模式生物中进行研究的，直到最近，才通过微图案化技术在人类特定背景下开展研究。微图案化技术揭示了模式形成和胚层特化过程中的机制；然而，细胞分选及其在特定胚层组合中的分离情况尚未在人类特定系统中得到研究。在这里，我们开发了一种人类外胚层模式形成模型，其中人类多能干细胞（hPSC）自我组织形成径向区域化的神经和非中枢神经系统（CNS）外胚层。我们表明，通过使用微图案化技术并调节BMP和WNT信号，我们可以调节不同外胚层群体的出现和空间分布。这种预先模式化的外胚层可用于研究hPSC衍生的中内胚层细胞的细胞分选行为，其中内胚层与神经外胚层分离。因此，微技术与胚层交叉混合的结合能够在人类背景下研究不同胚层的细胞分选。
