Astrocytes originated from neural stem cells drive the regenerative remodeling of pathologic CSPGs in spinal cord injury.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-19 DOI:10.1016/j.stemcr.2024.08.007
Seyed Mojtaba Hosseini, Shiva Nemati, Soheila Karimi-Abdolrezaee
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引用次数: 0

Abstract

Neural degeneration is a hallmark of spinal cord injury (SCI). Multipotent neural precursor cells (NPCs) have the potential to reconstruct the damaged neuron-glia network due to their tri-lineage capacity to generate neurons, astrocytes, and oligodendrocytes. However, astrogenesis is the predominant fate of resident or transplanted NPCs in the SCI milieu adding to the abundant number of resident astrocytes in the lesion. How NPC-derived astrocytes respond to the inflammatory milieu of SCI and the mechanisms by which they contribute to the post-injury recovery processes remain largely unknown. Here, we uncover that activated NPC-derived astrocytes exhibit distinct molecular signature that is immune modulatory and foster neurogenesis, neuronal maturity, and synaptogenesis. Mechanistically, NPC-derived astrocytes perform regenerative matrix remodeling by clearing inhibitory chondroitin sulfate proteoglycans (CSPGs) from the injury milieu through LAR and PTP-σ receptor-mediated endocytosis and the production of ADAMTS1 and ADAMTS9, while most resident astrocytes are pro-inflammatory and contribute to the pathologic deposition of CSPGs. These novel findings unravel critical mechanisms of NPC-mediated astrogenesis in SCI repair.

源自神经干细胞的星形胶质细胞推动了脊髓损伤中病理性 CSPG 的再生重塑。
神经变性是脊髓损伤(SCI)的标志。多能神经前体细胞(NPCs)具有生成神经元、星形胶质细胞和少突胶质细胞的三系能力,因此有可能重建受损的神经元-胶质细胞网络。然而,在 SCI 环境中,星形胶质细胞的形成是常住或移植 NPC 的主要命运,这使得病变部位常住星形胶质细胞的数量更加丰富。NPC衍生的星形胶质细胞如何对SCI的炎症环境做出反应以及它们对损伤后恢复过程做出贡献的机制在很大程度上仍是未知数。在这里,我们发现活化的 NPC 衍生星形胶质细胞表现出独特的分子特征,具有免疫调节作用并能促进神经发生、神经元成熟和突触生成。从机制上讲,NPC衍生的星形胶质细胞通过LAR和PTP-σ受体介导的内吞作用以及ADAMTS1和ADAMTS9的产生,清除损伤环境中的抑制性硫酸软骨素蛋白多糖(CSPGs),从而进行再生基质重塑,而大多数常驻星形胶质细胞则具有促炎作用,并导致CSPGs的病理性沉积。这些新发现揭示了在 SCI 修复中 NPC 介导的星形胶质细胞生成的关键机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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