洛克菲勒大学曹俊越小组宣布他们研究出基于IRISeq的无光学空间基因组学用于哺乳动物脑衰老图谱。这一研究成果发表在2026年5月12日出版的国际学术期刊《自然—神经科学》上。

在这里，该课题组研究人员介绍了成像重建主题索引测序（IRISeq）：一个无光学的，具有成本效益的平台，利用索引测序的空间相互作用映射来绘制可调节尺寸和分辨率（5-50 μm）的组织。该研究团队应用IRISeq绘制了70多个成人和老年无母主题大脑冠状切片的基因表达图谱，包括野生型和两种淋巴细胞缺陷模型（Rag1和Prkdc突变体），并生成了超过46万个空间转录组图谱。他们对783264个单细胞转录组的综合分析揭示了淋巴细胞依赖的区域特异性衰老特征，特别是在淋巴细胞耗竭时干扰素信号和脑室区域炎症的下调，以及突变特异性衰老途径的上调。

此外，淋巴细胞缺乏与脑室室管膜细胞的保留丰度和不同的小胶质细胞状态动力学有关，突出了淋巴细胞在脑衰老过程中驱动炎症过程中的关键作用。总的来说，IRISeq为空间解析转录组分析提供了高通量和高成本效益的解决方案，为阐明衰老背后的区域特异性细胞机制和确定保持大脑稳态的潜在治疗靶点开辟了新的途径。

研究人员表示，空间转录组学已经成为细胞异质性和相互作用原位作图的一种变革性方法，然而现有的方法往往会损害吞吐量、成本和组织覆盖。

附：英文原文

Title: Optics-free spatial genomics for mapping mammalian brain aging by IRISeq

Author: Abdulraouf, Abdulraouf, Jiang, Weirong, Zhang, Zehao, Xu, Zihan, Lu, Ziyu, Merlinsky, Tiffany, Liao, Andrew, Doymaz, Ahmet, Isakov, Samuel, Raihan, Tanvir, Zhou, Wei, Cao, Junyue

Issue&Volume: 2026-05-12

Abstract: Spatial transcriptomics has emerged as a transformative approach for in situ mapping of cellular heterogeneity and interactions, yet existing methods often compromise throughput, cost and tissue coverage. Here we introduce Imaging Reconstruction using Indexed Sequencing (IRISeq): an optics-free, cost-effective platform that leverages spatial interaction mapping by indexed sequencing to profile tissues at adjustable sizes and resolutions (5–50μm). We applied IRISeq to map gene expression across more than 70 coronal sections from both adult and aged mouse brains, including wild-type and two lymphocyte-deficient models (Rag1 and Prkdc mutants) and generated more than 460,000 spatial transcriptome profiles. Our integrated analysis with 783,264 single-cell transcriptomes revealed region-specific aging signatures that are lymphocyte dependent, notably a downregulation of interferon signaling and inflammation in ventricular regions upon lymphocyte depletion, alongside mutant-specific upregulation of senescence pathways. Furthermore, lymphocyte deficiency was linked to preserved abundance of ependymal cells that line the brain’s ventricles and to distinct microglial state dynamics, highlighting a key role for lymphocytes in driving inflammatory processes during brain aging. Overall, IRISeq provides a high-throughput and cost-effective solution for spatially resolved transcriptomic profiling, opening new avenues for elucidating region-specific cellular mechanisms underlying aging and identifying potential therapeutic targets to preserve brain homeostasis.

DOI: 10.1038/s41593-026-02293-1

Source: https://www.nature.com/articles/s41593-026-02293-1