Scalable longitudinal imaging and transcriptomics of cells in dynamic enclosures

  • bioRxiv. 2026 May 8:2026.05.05.723030. doi: 10.64898/2026.05.05.723030.
Tarun K Khurana  1 ,  Liz Y Wu  1 ,  Pier Federico Gherardini  1 ,  Seyedsina Moeinzadeh  1 ,  Mehdi Mohseni  1 ,  Filiz Gorpe Yasar  1 ,  Roger Dettloff  1 ,  Justin Poelma  1 ,  Shan Sabri  1 ,  Annarita Scaramozza  1 ,  Yunmin Li  1 ,  Nirvan Rouzbeh  1 ,  Nicholas Elder  1 ,  Shreya Deshmukh  1 ,  Alireza Majd  2 ,  Ria Gupta  1 ,  Sina Farahvashi  1 ,  Isaac Thomas  1 ,  Craig Betts  1 ,  Frank Charbonier  1 ,  David Roberts  1 ,  Pei-Lin Hsiung  1 ,  Eloise Zargari-Pariset  1 ,  Richard Yau  1 ,  Olaia F Vila  1 ,  Molly Phillips  1 ,  Carmen Xiao  1 ,  Jie Wang  1 ,  Yiqi Zhou  1 ,  Punam Adhikari  1 ,  Meng Taing  1 ,  Elaheh Farjami  1 ,  Behnam Javanmardi  1 ,  Merek Siu  1 ,  Cellanome Development Team ,  Camilla Valente  3 ,  Chris Cox  4 ,  Kathryn Geiger-Schuller  4 ,  Shannon J Turley  4  5 ,  Orit Rozenblatt-Rosen  4 ,  Faranak Fattahi  2 ,  Joseph R Ecker  6 ,  Jeffrey R Jones  7 ,  Fred H Gage  7 ,  Matthew H Spitzer  3  8  9 ,  Jasmine Pritchard  1 ,  Ilya Kupershmidt  1 ,  Peter Lundberg  1 ,  Shawn Levy  1 ,  Omead Ostadan  1 ,  Gary P Schroth  1 ,  Mostafa Ronaghi  1
Affiliations
  • 1. Cellanome Inc., Foster City, CA 94404, USA.
  • 2. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3. Department of Otolaryngology - Head and Neck Surgery and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 4. Genentech Inc., South San Francisco, CA 94080, USA.
  • 5. Present address: Amgen, Inc., Thousand Oaks, CA, USA.
  • 6. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • 7. Laboratory of Genetics LOG-G, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • 8. Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
  • 9. Gladstone-UCSF Institute for Genomic Immunology, San Francisco, CA 94158, USA.
PMID: 42146668 DOI: 10.64898/2026.05.05.723030
Abstract

Dynamic transitions between cell states underlie both normal physiology and disease. However, most single-cell technologies capture only static snapshots. To address this gap, we developed a platform that integrates light-guided hydrogel polymerization with computer vision to generate on-demand compartments around live cells, enabling longitudinal imaging of cellular behavior paired with whole-transcriptome profiling of the same cells at scale. These data link dynamic phenotypes with molecular programs, enabling deeper characterization of cellular states. This approach revealed an adaptive, drug-resistant state in lung Cancer cells characterized by Potassium Channel upregulation and p53-dependent quiescence. In models of adipogenesis and microglial phagocytosis, joint analysis of imaging and transcriptomic data identified key drivers of cellular function that were missed by transcriptomic clustering alone. These results establish the value of paired functional and transcriptomic analysis to resolve molecular drivers of complex cellular behaviors.

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