北京大学曾泽贤与清华大学潘登、华大生命科学研究院冯驭团队在研究中取得进展。他们发现利用CRISPR屏幕测序揭示空间分辨功能基因组学。这一研究成果于2026年5月26日发表在国际顶尖学术期刊《细胞》上。

为了解决这个问题，研究小组开发了空间CRISPR筛选测序（SPAC-seq），这是一个高通量空间CRISPR筛选平台，以及TARDIS（空间组学中扰动数据的目标优先化工具包），这是一个统计空间扰动分析工具包。利用SPAC-seq和TARDIS，该研究团队将基因扰动与空间表型和途径联系起来，揭示了肿瘤细胞中Icam1缺失如何通过免疫抑制和巨噬细胞极化促进转移。在CD8⁺ T细胞中，该研究团队发现Cd44通过与巨噬细胞上的Spp1相互作用来调节空间表型。该团队还展示了转录因子-趋化因子受体轴耦合细胞状态与趋化性的模型。SPAC-seq和TARDIS为研究不同生物和疾病背景下的空间解析功能基因组学和途径提供了一个有效的框架。

据了解，空间组学提高了他们对组织水平生物学的理解，然而，将基因功能扰动与空间表型和信号通路系统地联系起来的工具仍然有限。

附：英文原文

Title: Uncovering spatially resolved functional genomics with CRISPR screen sequencing

Author: Haorui Zhang, Zongxu Zhang, Peiyu Wang, Tian Xu, Xiaoyu Chen, Yanping Zhao, Siyu Lin, Wenjie Cai, Pengfei Ren, Ce Luo, Peng Zhang, Yunfeng Wang, Sen Hou, Yahui Zhao, Hu Zeng, Zhihua Liu, Cunyu Wang, Zhidong Gao, Yu Feng, Deng Pan, Zexian Zeng

Issue&Volume: 2026-05-26

Abstract: Spatial omics has advanced our understanding of tissue-level biology, yet tools to systematically link gene functional perturbations to spatial phenotypes and signaling pathways remain limited. To address this, we developed spatial CRISPR screen sequencing (SPAC-seq), a high-throughput spatial CRISPR screen platform, and TARDIS (target prioritization toolkit for perturbation data in spatial omics), a statistical spatial perturbation analysis toolkit. Using SPAC-seq and TARDIS, we linked gene perturbations to spatial phenotypes and pathways, uncovering how Icam1 loss in tumor cells promotes metastasis via immune suppression and macrophage polarization. In CD8+ T cells, we revealed Cd44’s role in regulating spatial phenotypes by interacting with Spp1 on macrophages. We also demonstrated the model of the transcription factor-chemokine receptor axis coupling cell states with chemotaxis. SPAC-seq and TARDIS provide an effective framework to study spatially resolved functional genomics and pathways across diverse biological and disease contexts.

DOI: 10.1016/j.cell.2026.04.049

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00516-7