人类神经类器官模型已成为研究神经生物学的重要工具。然而，提高此类类器官中神经细胞群的代表性仍然是一项重大工作。在这项工作中，我们将市售基质 Matrigel 与用于培养皮质神经类器官的神经钙粘蛋白 (N-cadherin) 肽功能化明胶甲基丙烯酰水凝胶（称为 GelMA-Cad）进行了比较。我们确定肽呈递可以在分化过程中调节明胶基质中的细胞命运和多样性。特别值得注意的是，与 Matrigel 相比，在 GelMA-Cad 水凝胶中培养的皮质类器官与人类胎儿群体的映射更接近，并且产生具有更多自发兴奋性突触后电流的神经元。这些结果提供了令人信服的证据，表明基质束缚的信号肽可以影响神经类器官的分化，为控制干细胞的命运开辟了一条途径。此外，这项工作的成果展示了 GelMA-Cad 作为一种简单且明确的水凝胶替代基质胶的技术实用性，用于神经类器官培养。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. We determined that peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad hydrogels mapped more closely to human fetal populations and produced neurons with more spontaneous excitatory postsynaptic currents relative to Matrigel. These results provide compelling evidence that matrix-tethered signaling peptides can influence neural organoid differentiation, opening an avenue to control stem cell fate. Moreover, outcomes from this work showcase the technical utility of GelMA-Cad as a simple and defined hydrogel alternative to Matrigel for neural organoid culture.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.