Cederquist Gustav Y, Oberst Polina, Chang Xuyao, Tchieu Jason, Studer Lorenz
The Center for Stem Cell Biology, Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Methods Mol Biol. 2025;2910:37-51. doi: 10.1007/978-1-0716-4446-1_3.
Human pluripotent stem cells (hPSCs) have the potential to differentiate into all human somatic cell types allowing for an experimental platform to access otherwise inaccessible tissues through directed differentiation protocols. Access to tissue is especially critical for neurobiology where functional human tissue is rare. The prefrontal cortex is an evolutionarily expanded addition to the cerebral cortex, associated with higher order cognitive function. Here, we present a method to generate neural progenitors and post-mitotic neurons with a prefrontal cortical identity through the directed differentiation of hPSCs under defined conditions. Neural induction is achieved by inhibiting TGF beta and BMP signaling (termed dual-SMAD inhibition) and neural progenitors are subsequently patterned toward the prefrontal cortex lineage using recombinant FGF8. Cells generated using this protocol open possibilities to study the unique developmental and synaptic properties of the prefrontal cortex, as well as to understand its selective vulnerability in a number of human brain disorders.
人类多能干细胞（hPSCs）有潜力分化为所有人类体细胞类型，从而提供了一个实验平台，通过定向分化方案来获取难以获得的组织。获取组织对于神经生物学尤为关键，因为功能性人类组织非常罕见。前额叶皮层是大脑皮层进化扩展的部分，与高级认知功能相关。在此，我们展示了一种在特定条件下通过hPSCs的定向分化来生成具有前额叶皮层特征的神经祖细胞和有丝分裂后神经元的方法。通过抑制转化生长因子β（TGF beta）和骨形态发生蛋白（BMP）信号传导（称为双SMAD抑制）实现神经诱导，随后使用重组成纤维细胞生长因子8（FGF8）将神经祖细胞诱导为前额叶皮层谱系。使用该方案生成的细胞为研究前额叶皮层独特的发育和突触特性以及了解其在多种人类脑部疾病中的选择性易损性开辟了可能性。
