Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF induction led to progenitor expansion, an increased number of upper cortical neurons and glia, and enhanced motor and social behavior in adult mice. Additionally, controlled YF induction is tolerated by principal neurons in the adult dorsal hippocampus and prevented the development of several hallmarks of Alzheimer’s disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model. These results highlight the powerful impact of YFs on neural proliferation and their potential use in brain disorders.

中文翻译：

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通过体内瞬时重编程扩展新皮层并防止神经退行性变


山中因子 （YF） 可以逆转哺乳动物组织中的一些衰老特征，但它们对大脑的影响在很大程度上仍未得到探索。在这里，我们在两种不同的情况下以受控的时空方式在小鼠大脑中诱导 YFs：神经退行性变背景下的大脑发育和成人阶段。YFs 的胚胎诱导扰乱了祖细胞和神经元的细胞身份，但这些细胞可以耐受瞬时和低水平表达。在这些情况下，YF 诱导导致成年小鼠的祖细胞扩增、上皮层神经元和神经胶质细胞数量的增加以及运动和社会行为的增强。此外，在 5xFAD 小鼠模型中，成人背侧海马体中的主要神经元可耐受受控的 YF 诱导，并防止阿尔茨海默病的几个标志的发展，包括认知能力下降和分子特征改变。这些结果突出了 YF 对神经增殖的强大影响及其在脑部疾病中的潜在用途。