2025-12-02 イェール大学
<関連情報>
- https://news.yale.edu/2025/12/02/shining-brighter-light-link-between-cells-and-disease
- https://www.cell.com/developmental-cell/fulltext/S1534-5807(25)00666-5
顕微鏡ベースのCRISPRスクリーニングプラットフォームは、オルガネラの機能ゲノミクスを可能にし、繊毛生物学を解明します A microscopy-based CRISPR screening platform enables organellar functional genomics and illuminates ciliary biology
Jingbo Sun ∙ Irem Sude Atiş ∙ Stéfany L.L. Empke ∙ Mustafa K. Khokha ∙ David K. Breslow
Developmental Cell Published:November 20, 2025
DOI:https://doi.org/10.1016/j.devcel.2025.10.015
Graphical abstract
Highlights
- Development of a pooled CRISPR screening platform for microscopy-based phenotypes
- An accessible workflow supports live-cell or antibody-based molecular markers
- Genome-wide and targeted screens reveal novel regulators of primary cilia
- SMIM27/TZMP1 is a transition zone microprotein needed for ciliogenesis
Summary
Microscopy offers an indispensable technique for visualizing biological processes and for defining cytological abnormalities characteristic of disease. However, combining microscopy with the power of pooled CRISPR screening presents considerable technical challenges, hindering application of systematic genetic analysis to imaging-defined phenotypes. Here, we establish a fluorescence microscopy-based CRISPR screening platform that combines ease of implementation with flexible analysis of live-cell or antibody-based molecular markers, including post-translational modifications. Applying this methodology, we systematically identify regulators of primary cilium structure and function in human cells through targeted and genome-wide screens. We further show that integration of screens focused on distinct ciliary phenotypes yields multi-dimensional profiles that delineate precise gene functions. Among the identified hits, TZMP1 (SMIM27) encodes a microprotein at the ciliary transition zone that is required for ciliogenesis in human cells and for ciliary function in Xenopus embryos. More broadly, our approach provides a technological and conceptual strategy for microscopy-based functional genomics.
