2026-10-07 ミュンヘン大学（LMU）
＜関連情報＞
- https://www.lmu.de/en/newsroom/news-overview/news/tracking-down-cellular-gene-functions-with-ai-and-microscopy-c3951c14.html
- https://www.cell.com/cell/fulltext/S0092-8674(26)01123-2
SPARCSは、遺伝子スクリーニングのための複雑な画像ベースの表現型のスケーラブルな復元を可能にする SPARCS enables scalable recovery of complex image-based phenotypes for genetic screening
Niklas A. Schmacke ∙ Sophia C. Mädler ∙ Georg Wallmann ∙ … ∙ Fabian J. Theis ∙ Matthias Mann ∙ Veit Hornung
Cell Published:October 6, 2026
DOI:https://doi.org/10.1016/j.cell.2026.09.021
Highlights
- SPARCS enables image-based CRISPR screening of complex phenotypes at scale
- AI guides recovery of mutant cells in situ by automated laser microdissection
- Genome-wide screens in 70 million cells reveal regulators of autophagy and STING signaling
- Profiling isolated hits by mass spectrometry proteomics maps pathways driving phenotypes
Summary
Forward genetic screening links genotype to phenotype by introducing random genetic perturbations and identifying phenotype-altering mutations. Although genome-scale screens are routine for simple phenotypes in cultured cells, extending them to complex image-based phenotypes remains challenging. Here, we present spatially resolved CRISPR screening (SPARCS), a microscopy-based platform for forward genetic screening on single-cell images. SPARCS physically isolates mutants in situ by automated laser microdissection, enabling image-based screening at unprecedented scale with multimodal hit phenotyping. We demonstrate SPARCS in genome-wide CRISPR knockout screens of autophagosome formation and activation of the immune sensor STING across 70 million cells. Via machine learning-based image analysis, SPARCS recovered most macroautophagy genes and identified GPHR as a pH-dependent regulator of STING. Mass spectrometry-based proteomics of isolated hit cells revealed endoplasmic reticulum (ER)/Golgi disruption and nominated additional STING regulators via in silico perturbation modeling. These results establish SPARCS as a scalable platform for genome-wide genetic screening of complex cellular phenotypes with a proteome-level readout.
