脳の発達と炎症解決過程をマルチマップで解明(Scientists Map How the Brain Develops and Resolves Inflammation)

2025-11-07

2025-11-06 カロリンスカ研究所(KI)

カロリンスカ研究所とイェール大学の国際チームは、マウス脳の発達過程と炎症応答を多次元で解析できる新手法「空間トリオミクス(spatial tri-omics)」を開発し、出生後から若年期にかけての遺伝子発現・エピジェネティクス・タンパク質生成を同時可視化した。結果、発達期に働く分子プログラムが炎症時に再活性化されることを発見し、神経炎症が脳内で局所にとどまらず遠隔部位へ波及することを確認。これは多発性硬化症(MS)などでの髄鞘破壊機構理解につながる知見である。成果はNature誌に掲載。

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脳の発達と神経炎症の空間ダイナミクス Spatial dynamics of brain development and neuroinflammation

Di Zhang,Leslie A. Rubio Rodríguez-Kirby,Yingxin Lin,Wenqi Wang,Mengyi Song,Li Wang,Lijun Wang,Shigeaki Kanatani,Tony Jimenez-Beristain,Yonglong Dang,Mei Zhong,Petra Kukanja,Shuozhen Bao,Shaohui Wang,Xinyi Lisa Chen,Fu Gao,Dejiang Wang,Hang Xu,Cong Ma,Xing Lou,Yang Liu,Jinmiao Chen,Nenad Sestan,Per Uhlén,… Rong Fan
Nature Published:05 November 2025
DOI:https://doi.org/10.1038/s41586-025-09663-y

Abstract

The ability to spatially map multiple layers of omics information across developmental timepoints enables exploration of the mechanisms driving brain development¹, differentiation, arealization and disease-related alterations. Here we used spatial tri-omic sequencing, including spatial ATAC–RNA–protein sequencing and spatial CUT&Tag–RNA–protein sequencing, alongside multiplexed immunofluorescence imaging (co-detection by indexinng (CODEX)) to map dynamic spatial remodelling during brain development and neuroinflammation. We generated a spatiotemporal tri-omic atlas of the mouse brain from postnatal day 0 (P0) to P21 and compared corresponding regions with the human developing brain. In the cortex, we identified temporal persistence and spatial spreading of chromatin accessibility for a subset of layer-defining transcription factors. In the corpus callosum, we observed dynamic chromatin priming of myelin genes across subregions and identified a role for layer-specific projection neurons in coordinating axonogenesis and myelination. In a lysolecithin neuroinflammation mouse model, we detected molecular programs shared with developmental processes. Microglia exhibited both conserved and distinct programs for inflammation and resolution, with transient activation observed not only at the lesion core but also at distal locations. Overall, this study reveals common and differential mechanisms underlying brain development and neuroinflammation, providing a rich resource for investigating brain development, function and disease.