Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen 518055, China; Tsinghua-Berkeley Shenzhen Institute, Shenzhen 518055, China.
Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen 518055, China; Tsinghua-Berkeley Shenzhen Institute, Shenzhen 518055, China.
Cell Syst. 2023 Oct 18;14(10):872-882.e3. doi: 10.1016/j.cels.2023.09.004. Epub 2023 Oct 10.
Although biochemical regulation has been extensively studied in organoid modeling protocols, the role of mechanoregulation in directing stem cell fate and organoid development has been relatively unexplored. To accurately replicate the dynamic organoid development observed in nature, in this study, we present a method of heterogeneous embedding using an alginate-shell-Matrigel-core system. This approach allows for cell-Matrigel remodeling by the inner layer and provides short-term moderate-normal compression through the soft alginate outer layer. Our results show that the time-limited confinement contributes to increased expression of neuronal markers such as neurofilament (NF) and microtubule-associated protein 2 (MAP2). Compared with non-alginate embedding and alginate compression groups, volume growth remains unimpeded. Our findings demonstrate the temporary mechanical regulation of cerebral organoid growth, which exhibits a regular growth profile with enhanced maturation. These results highlight the importance and potential practical applications of mechanoregulation in the establishment of brain organoids. A record of this paper's transparent peer review process is included in the supplemental information.
虽然在类器官建模方案中已经广泛研究了生化调节，但机械调节在指导干细胞命运和类器官发育中的作用仍相对未知。为了准确复制自然界中观察到的动态类器官发育，在本研究中，我们提出了一种使用藻酸盐壳-基质核心系统的异质包埋方法。这种方法允许内层细胞重塑基质，并通过柔软的藻酸盐外层提供短期适度的正常压缩。我们的结果表明，限时约束有助于增加神经元标志物如神经丝（NF）和微管相关蛋白 2（MAP2）的表达。与非藻酸盐包埋和藻酸盐压缩组相比，体积生长不受阻碍。我们的发现表明，脑类器官生长受到暂时的机械调节，表现出有规律的生长模式和增强的成熟度。这些结果突出了机械调节在建立大脑类器官中的重要性和潜在的实际应用。本文透明同行评审过程的记录包含在补充信息中。
