Resources: Publications
Linking live-cell behavior to transcriptional responses across perturbations using dynamic caging
May 5, 2026
BioRxiv
Authors
Brian Orcutt-Jahns, Raúl A. Reyes Hueros, Ana M. Meireles, Christian Cox, Luca Ghita, Jack Kamm, Cemre Celen, Yiming Yang, Eloise Zargari-Pariset, Nirvan Rouzbeh, Yiqi Zhou, Jie Wang, Shan Sabri, Takamasa Kudo, Pratiksha I. Thakore, David Richmond, Tommaso Biancalani, Hye-Jung Kim, Pier Federico Gherardini, Gary P. Schroth, Shannon J. Turley, Orit Rozenblatt-Rosen, Hector Corrada Bravo, Bo Li, Kathryn Geiger-Schuller
Scientific Summary
Led by researchers at Genentech in collaboration with Cellanome scientists, this preprint demonstrates how paired longitudinal imaging, transcriptomics, protein measurements, and CRISPR perturbation screening can be combined to investigate cellular responses across multiple experimental systems. Researchers applied the workflow to human regulatory T cells (Tregs), human colonic fibroblasts, and CRISPR-perturbed macrophages, enabling direct comparison of cellular behavior with molecular state in the same individual cells.
Across these studies, the integrated measurements revealed biological relationships that would have been difficult to identify using transcriptomics or imaging alone. Morphological features were linked directly to transcriptional programs, protein expression provided functional context for gene expression, and pooled CRISPR perturbations connected gene function to coordinated changes in morphology, protein abundance, and transcriptional state.
Together, the work illustrates how combining complementary single-cell measurements can provide a more complete view of cellular responses to perturbation and help identify functional phenotypes that emerge only when multiple data modalities are analyzed together.
Key Highlights
- Demonstrated integrated longitudinal analysis across three biological systems: human regulatory T cells, human colonic fibroblasts, and pooled CRISPR perturbation screens in macrophages.
- Linked live-cell morphology, protein expression, and whole-transcriptome measurements from the same individual cells, enabling direct comparison of cellular behavior with molecular state.
- Identified relationships between cellular morphology and transcriptional programs, including associations between Treg morphology and suppressive gene signatures, and fibroblast morphology and inflammatory states.
- Showed that protein measurements provided functional information complementary to transcriptomics, revealing immune-associated cellular states that were not fully explained by RNA expression alone.
- Introduced PERTURB-LINK, a pooled CRISPR screening workflow that connected individual genetic perturbations with corresponding changes in morphology, protein expression, and transcriptional state within the same cells.
- Mapped functional regulators of the NF-κB pathway by integrating transcriptomic, proteomic, and imaging measurements, revealing perturbation-specific phenotypes across multiple cellular modalities.
- Demonstrated how paired multimodal measurements can reveal biological relationships that may remain hidden when molecular or phenotypic measurements are analyzed independently.
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