Spatiotemporal remodeling of cytoskeletal and junction networks during somatic cell reprogramming

Samson, R.; Kitaygorodsky, J.; Tersigni, M.; Tursun, T.; Hu, Q.; Hardy, W. R.; Trcka, D.; Rost, H.; Wrana, J. L.; Samavarchi-Tehrani, P.; Gingras, A.-C.

doi:10.64898/2026.05.26.725436

bioRxiv · 10.64898/2026.05.26.725436

Spatiotemporal remodeling of cytoskeletal and junction networks during somatic cell reprogramming

Samson, R.·Kitaygorodsky, J.·Tersigni, M.·Tursun, T.·Hu, Q.·Hardy, W. R.·Trcka, D.·Rost, H.·Wrana, J. L.·Samavarchi-Tehrani, P.·Gingras, A.-C.

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Abstract

Summary/AbstractReprogramming somatic cells into induced pluripotent stem cells involves a dramatic reorganization of the cytoskeleton and junctions during the critical mesenchymal-to-epithelial transition stage. While protein abundance changes have been profiled, the spatiotemporal dynamics of protein-protein associations involving these structural components remain poorly resolved. Here, we present a time-resolved proximity proteomics resource that maps cytoskeletal and junctional remodeling across 27 baits during the early stages of reprogramming. We identified over 1100 high-confidence interactions, including many not previously reported, capturing the dynamic reorganization of cell architecture. By integrating proximity-dependent biotinylation with quantitative proteomics, we distinguished spatial relocalizations from abundance-driven effects. Dynamic redistributions of actin regulators and desmosomal proteins were observed, and a targeted short interfering RNA screen uncovered early acting structural proteins essential for colony formation. Our findings reveal adhesion and cytoskeletal maturation as structural bottlenecks in reprogramming and provide a broadly applicable framework for mapping subcellular remodeling during dynamic cell fate transitions.

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Samson, R., Kitaygorodsky, J., Tersigni, M., Tursun, T., Hu, Q., Hardy, W. R., Trcka, D., Rost, H., Wrana, J. L., Samavarchi-Tehrani, P., Gingras, A.-C.. 2026-05-28. Spatiotemporal remodeling of cytoskeletal and junction networks during somatic cell reprogramming. https://doi.org/10.64898/2026.05.26.725436

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