PDF(Pubmed)
Abstract：
Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.
摘要：
合成Notch（synNotch）受体是基因编码的，模块化合成受体，使哺乳动物细胞能够检测环境信号并通过激活用户规定的转录程序来响应。尽管一些材料已被修改以提供具有粗略空间控制的synNotch配体，在组织工程中的应用通常需要细胞外基质(ECM)衍生的支架和/或多个配体的更精细的空间定位。因此，我们在这里开发了一套激活synNotch受体的材料，用于材料到细胞信号传导的普遍工程。我们基因和化学融合功能性synNotch配体到ECM蛋白和ECM衍生材料。我们还通过在用两个synNotch配体微接触印刷的表面上用两个正交synNotch程序培养细胞，在四个不同的报告表型上产生具有微型精度的组织。最后,我们通过在用户定义的微模式中将成纤维细胞共转分化为骨骼肌或内皮细胞前体来展示其在组织工程中的应用。这些技术为空间控制哺乳动物组织中的细胞表型提供了途径。
