生物功能化明胶水凝胶支持IPSC衍生的皮质器官的发展和成熟
Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids
影响因子:6.90000
分区:生物学1区 Top / 细胞生物学2区
发表日期:2024 Nov 26
作者:
Andrew Kjar, Mia R Haschert, José C Zepeda, A Joey Simmons, Alexis Yates, Daniel Chavarria, Melanie Fernandez, Gabriella Robertson, Adam M Abdulrahman, Hyosung Kim, Nicole T Marguerite, Rachel K Moen, Lauren E Drake, Corinne W Curry, Brian J O'Grady, Vivian Gama, Ken S Lau, Brad Grueter, Jonathan M Brunger, Ethan S Lippmann
摘要
人类神经器官模型已成为研究神经生物学的重要工具。但是，改善此类类器官中神经细胞群体的代表性仍然是一项重大努力。在这项工作中，我们将Matrigel（一种市售基质）与神经钙粘蛋白（N-钙粘蛋白）肽官能化的明胶甲基丙烯酰水凝胶（称为Gelma-CAD）进行培养皮质神经类器官。我们确定肽表现可以调节分化过程中明胶基质中的细胞命运和多样性。尤其值得注意的是，在凝胶型水凝胶中培养的皮质器官更紧密地映射到人类胎儿群体，并产生神经元，具有相对于基质凝胶的更自发兴奋性突触后电流。这些结果提供了令人信服的证据，表明基质螺旋的信号传导肽可以影响神经器官的分化，从而为控制干细胞的命运开辟了道路。此外，这项工作的结果展示了Gelma-CAD作为神经类器官培养的简单且定义的水凝胶替代品的技术实用性。
Abstract
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.