Outer radial glia promotes white matter regeneration after neonatal brain injury.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-02-28 DOI:10.1016/j.xcrm.2025.101986

Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo

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Abstract

The developing gyrencephalic brain contains a large population of neural stem cells in the ventricular zone and outer subventricular zone (OSVZ), the latter populated by outer radial glia (oRG). The role of oRG during postnatal development is not well understood. We show that oRG cells increase proliferative capacity and contribute to oligodendrocyte precursor cell (OPC) production following brain injury in human infants and neonatal piglets, whose brains resemble the human brain in structure and development. RNA sequencing revealed oRG-specific transcriptional responses to injury in piglets and showed that the activating transcription factor 5 (ATF5) pathway positively regulates oRG proliferation. Intranasal activation of ATF5 using salubrinal enhanced OSVZ-derived oligodendrogenesis in the injured periventricular white matter and improved functional recovery. These results reveal a key role for postnatal oRG in brain injury recovery and identify ATF5 as a potential therapeutic target for treating white matter injury in infants.

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外放射状胶质细胞促进新生儿脑损伤后白质再生。

发育中的脑回畸形在脑室区和外室下区（OSVZ）含有大量的神经干细胞，后者由外放射状胶质细胞（oRG）填充。oRG在出生后发育中的作用尚不清楚。我们发现，人类婴儿和新生仔猪脑损伤后，oRG细胞增加了增殖能力，促进了少突胶质前体细胞（OPC）的产生，这些婴儿和新生仔猪的大脑在结构和发育上与人类大脑相似。RNA测序揭示了仔猪oRG对损伤的特异性转录反应，并表明激活转录因子5 （ATF5）通路正调控oRG的增殖。鼻内使用盐水激活ATF5可增强受损脑室周围白质中osvz来源的少突胶质形成，并改善功能恢复。这些结果揭示了出生后oRG在脑损伤恢复中的关键作用，并确定了ATF5作为治疗婴儿白质损伤的潜在治疗靶点。

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

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.