Spatial perturb-seq: single-cell functional genomics within intact tissue architecture
We develop Spatial Perturb-Seq, an in vivo CRISPR technology that interrogates multiple genes within single cells of intact tissues, compatible with both sequencing-based and probe-based spatial technologies. We apply Spatial Perturb-Seq to knock out risk genes for neurodegenerative diseases in the mouse brain, uncovering cell autonomous and cell-cell microenvironmental effects within the spatially intact tissue. Spatial Perturb-Seq functionally screens multiple genes in situ and in vivo, bypasses cell processing steps that skew cell type representation, identifies intracellular and intercellular effects of knockouts, and identifies candidate genes underlying dysregulated neuronal intercellular communication pathways.
Authors
- S. Prabhakar
- Ke Guo (ORCID: https://orcid.org/0000-0001-5681-2049)
- Daryl Shern Lim (ORCID: https://orcid.org/0000-0002-0489-4852)
- Kok Hao Chen (ORCID: https://orcid.org/0000-0001-7406-7919)
- Wan Yi Seow (ORCID: https://orcid.org/0000-0002-8438-048X)
- Muhammad Irfan Bin Hajis
- Bolun Wang (ORCID: https://orcid.org/0000-0002-8951-4002)
- Amine Meliani
- Wei Leong Chew
- Michelle Gek Liang Lim
- Kimberle Shen
- Choong Tat Keng
Institutions
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- National University Cancer Institute, Singapore (SG)
- Genome Institute of Singapore (SG)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-21
- DOI
- https://doi.org/10.1038/s41467-026-69677-6
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Medical Research Council
- National Medical Research Council