小柯机器人

美国宾夕法尼亚大学Hongjun Song和Guo-li Ming共同合作近期取得重要工作进展，他们研究开发出了人类海马未成熟神经元在整个生命期的分子图谱。相关研究成果2022年7月6日在线发表于《自然》杂志上。

在这里，研究人员在经过验证的基于机器学习分析方法的帮助下进行了单核RNA测序，以识别imGC并量化它们在人类海马生命周期不同阶段的丰度。他们确定了人类imGC在整个生命周期中的共同分子标志，并观察到人类imGC中与年龄相关的转录动力学，这表明细胞功能、生态位相互作用和疾病相关性的变化与小鼠不同。研究人员还发现阿尔茨海默病中基因表达改变的imGC数量减少。

最后，研究人员用罕见的齿状颗粒细胞脂肪特异性增殖的神经祖细胞的存在和培养的手术标本，证明了成年人类海马的神经发生能力。总之，他们的研究结果表明，成人海马体中存在大量imGCs，通过低频从头生成和长期成熟，研究人员揭示了imGCs在整个生命周期和阿尔茨海默病中的分子特性。

据介绍，由成年人海马神经发生产生的未成熟齿状颗粒细胞 (imGC) ，有助于啮齿动物的可塑性和独特的大脑功能，并且在多种人类神经系统疾病中失调。人们对成人海马imGCs的分子特征知之甚少，甚至它们的存在也受到争议。

附：英文原文

Title: Molecular landscapes of human hippocampal immature neurons across lifespan

Author: Zhou, Yi, Su, Yijing, Li, Shiying, Kennedy, Benjamin C., Zhang, Daniel Y., Bond, Allison M., Sun, Yusha, Jacob, Fadi, Lu, Lu, Hu, Peng, Viaene, Angela N., Helbig, Ingo, Kessler, Sudha K., Lucas, Timothy, Salinas, Ryan D., Gu, Xiaosong, Chen, H. Isaac, Wu, Hao, Kleinman, Joel E., Hyde, Thomas M., Nauen, David W., Weinberger, Daniel R., Ming, Guo-li, Song, Hongjun

Issue&Volume: 2022-07-06

Abstract: Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3,4,5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6,7,8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.

DOI: 10.1038/s41586-022-04912-w

Source: https://www.nature.com/articles/s41586-022-04912-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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