美国宾夕法尼亚大学Guo-li Ming，Hongjun Song和Yijing Su共同合作近期取得重要工作进展，他们绘制了出生后人类海马胶质细胞多样性的单细胞转录组图谱。相关研究成果2022年11月3日在线发表于《细胞—干细胞》杂志上。

研究人员进行单核RNA测序，生成整个出生后人类海马转录组图谱。对星形胶质细胞、少突胶质细胞谱系和小胶质细胞的详细分析确定了具有不同分子特征的亚群，并揭示它们与特定生理功能、年龄依赖性丰度变化和疾病相关性的关系。研究人员使用免疫组织学进一步表征了海马结构中，富含GFAP的星形胶质细胞亚群的时空异质性。

利用胶质细胞亚群分类作为参考图谱，研究人员揭示了从人类多能干细胞分化的胶质细胞的多样性，并确定了阿尔茨海默病（AD）中特定胶质细胞亚群中的失调基因和病理过程。总之，这一研究大大扩充了对人类胶质细胞多样性、出生后的种群动态以及AD相关调节异常的理解，并为基于干细胞的胶质细胞分化提供了参考图谱。

据介绍，人类海马中胶质细胞的分子多样性及其在寿命中的时间动态在很大程度上仍然未知。

附：英文原文

Title: A single-cell transcriptome atlas of glial diversity in the human hippocampus across the postnatal lifespan

Author: Yijing Su, Yi Zhou, Mariko L. Bennett, Shiying Li, Marc Carceles-Cordon, Lu Lu, Sooyoung Huh, Dennisse Jimenez-Cyrus, Benjamin C. Kennedy, Sudha K. Kessler, Angela N. Viaene, Ingo Helbig, Xiaosong Gu, Joel E. Kleinman, Thomas M. Hyde, Daniel R. Weinberger, David W. Nauen, Hongjun Song, Guo-li Ming

Issue&Volume: 2022/11/03

Abstract: The molecular diversity of glia in the human hippocampus and their temporal dynamicsover the lifespan remain largely unknown. Here, we performed single-nucleus RNA sequencingto generate a transcriptome atlas of the human hippocampus across the postnatal lifespan.Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identifiedsubpopulations with distinct molecular signatures and revealed their association withspecific physiological functions, age-dependent changes in abundance, and diseaserelevance. We further characterized spatiotemporal heterogeneity of GFAP-enrichedastrocyte subpopulations in the hippocampal formation using immunohistology. Leveragingglial subpopulation classifications as a reference map, we revealed the diversityof glia differentiated from human pluripotent stem cells and identified dysregulatedgenes and pathological processes in specific glial subpopulations in Alzheimer’s disease(AD). Together, our study significantly extends our understanding of human glial diversity,population dynamics across the postnatal lifespan, and dysregulation in AD and providesa reference atlas for stem-cell-based glial differentiation.

DOI: 10.1016/j.stem.2022.09.010

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00418-0