Zhou Qingsheng, Fang Qiongxuan, Zhang Chunming, Liu Wei, Sun Yifeng
Department of Spine Surgery, Yantaishan Hospital, Binzhou Medical University, 10087 Science and Technology Avenue, Yantai, Shandong, 264003, P. R. China.
MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, P. R. China.
Spinal Cord. 2025 May;63(5):263-269. doi: 10.1038/s41393-025-01077-x. Epub 2025 Apr 14.
An integrated bioinformatics data study.
This study, through bioinformatics analysis, aims to map the landscape of astrocytes, explore key signaling pathways, and uncover molecular mechanisms that support SCI recovery facilitated by MSCs and iPSCs.
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.
We performed a bioinformatics analysis of single-cell transcriptomes (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data sourced from Gene Expression Omnibus (GEO) datasets. The data processing involved R packages like "Seurat," "DESeq2," and "WGCNA." For pathway enrichment, we used Gene Set Enrichment Analysis (GSEA) and the Enrichr web server.
Single-cell and spatial transcriptomic analysis revealed notable changes in the astrocyte landscape after SCI, highlighting a significant disruption in astrocyte populations within the injured region. Findings suggest that BDNF regulation of GABA neurotransmission and GABA receptor signaling in astrocytes plays a key role in promoting neuronal regeneration. Additionally, hUC-MSCs were found to enhance neural repair by activating BDNF-regulated GABA signaling of astrocytes. A promising alternative involves iPS-derived MSCs, which have shown potential to boost neural regeneration through BDNF, GABA, and GABA receptor signaling pathways of astrocytes.
In summary, SCI disrupts astrocyte populations, impacting their ability to support neural repair. BDNF-regulated GABA signaling in astrocytes is essential for neuron regeneration. Both hUC-MSCs and iPS-derived MSCs show promise in enhancing neural recovery by activating these pathways, offering potential new therapeutic options for SCI.
一项综合生物信息学数据研究。
本研究通过生物信息学分析，旨在描绘星形胶质细胞图谱，探索关键信号通路，并揭示支持间充质干细胞（MSCs）和诱导多能干细胞（iPSCs）促进脊髓损伤（SCI）恢复的分子机制。
清华大学临床医学院北京清华长庚医院。
我们对来自基因表达综合数据库（GEO）数据集的单细胞转录组（scRNA-seq）、空间转录组学和批量RNA-seq数据进行了生物信息学分析。数据处理涉及“Seurat”“DESeq2”和“WGCNA”等R包。对于通路富集，我们使用了基因集富集分析（GSEA）和Enrichr网络服务器。
单细胞和空间转录组分析显示，SCI后星形胶质细胞图谱发生了显著变化，突出了损伤区域内星形胶质细胞群体的重大破坏。研究结果表明，星形胶质细胞中脑源性神经营养因子（BDNF）对γ-氨基丁酸（GABA）神经传递和GABA受体信号的调节在促进神经元再生中起关键作用。此外，发现人脐带间充质干细胞（hUC-MSCs）通过激活星形胶质细胞的BDNF调节的GABA信号来增强神经修复。一种有前景的替代方法涉及诱导多能干细胞衍生的间充质干细胞，其已显示出通过星形胶质细胞的BDNF、GABA和GABA受体信号通路促进神经再生的潜力。
总之，SCI破坏了星形胶质细胞群体，影响了它们支持神经修复的能力。星形胶质细胞中BDNF调节的GABA信号对于神经元再生至关重要。hUC-MSCs和诱导多能干细胞衍生的间充质干细胞在通过激活这些通路增强神经恢复方面都显示出前景，为SCI提供了潜在的新治疗选择。
