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<p>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.</p>

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Spatial perturb-seq: single-cell functional genomics within intact tissue architecture

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月21日

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  • Kimberle Shen,
  • Wan Yi Seow,
  • Choong Tat Keng,
  • Michelle Gek Liang Lim,
  • Daryl Shern Lim,
  • Ke Guo,
  • Amine Meliani,
  • Muhammad Irfan Bin Hajis,
  • Bolun Wang,
  • Shyam Prabhakar,
  • Kok Hao Chen,
  • Wei Leong Chew

摘要

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.