What is the name of the methodology?
Chromosomal instability (CIN)-seq: a targeted single-cell multi-omics method that selectively profiles rare live CIN phenotypes at scale
OI Name
Miao-Ping Chien group
What is the methodology good for?
The methodology is well suited for characterizing the temporal expression associated with live and spontaneous CIN events, specifically multipolar mitosis, micronuclei, and chromosomal bridging, which are usually difficult to capture with standard methods because they are rare, dynamic, and mixed within large cell populations.
What is/are the main advantages of this methodology over related technologies?
The main advantage of this methodology is that it only selects and profiles rare cells based on live phenotypic CIN events, assisted by real-time imaging analysis before sequencing, allowing direct linking of abnormal mitotic behavior to the corresponding genomic and transcriptomic states.
What are the most important limitations of the methodology?
A key limitation is that the method is not easily operational, as it requires a delicate real-time data acquisition-analysis pipeline. Specifically, it acquires spatiotemporal imaging data from up to millions of cells, performs real-time computation to identify and export cell subpopulations displaying CIN phenotypes, and then immediately applies selective photolabeling and sorting for downstream (single-cell) sequencing. The method also depends on visually identifiable CIN phenotypes; therefore, abnormalities that are subtle or difficult to classify under microscopy may be missed.
What type of samples are compatible with methodology?
Cancer cell lines | Primary cells in culture | 2D derived organoids | 3D derived organoids | Primary tissue |
Yes | Yes | Yes | Possibly | possibly |
What future develops to the methodology are you planning, in any?
Extending CIN-seq to additional omics modalities and 3D sample profiling.
If someone outside your lab wants to use the methodology, what is the best option?
The whole pipeline is somewhat challenging, as explained above. Therefore, collaboration with our group is recommended, at least until the selected cell subpopulations are collected. Afterward, users can proceed with their preferred omics profiling and analyses if needed.
Name one or more people in your lab that are experienced with the methodology
Ting-Chun Chou
Tsai-Ying Chen
Who originally developed the methodology?
Pin-Rui Su and Ting-Chun Chou. References below:
- Su, P.R.*, Chou, C.T.*, López-Cascales, M.T.**, Huang, J.**, Chen, T.-Y.**, van Wieren, S., Li, C., Beerens, C., You, L., Storteboom, J., Chien, M.P. “Unraveling the molecular mechanisms underlying spontaneous chromosomal instability through CIN-seq”. Advanced Science, In Press. 2026. doi: https://doi.org/10.64898/2025.12.24.696383.
- You L.*, Su P.R.*, Betjes M*. Ghadiri Rad, R., Chou, T.C., Beerens, C., van Oosten, E., Leufkens, F., Gasecka, P., Muraro, M., van Tol, R., van Steenderen, D., Farooq, S., Hardillo, J.A.U., Baatenburg de Jong, R., Brinks, D., Chien, M.P. “Linking the genotypes and phenotypes of cancer cells in heterogenous populations via real-time optical tagging and image analysis”, Nature Biomedical Engineering, 2022 (https://rdcu.be/cJct9) (https://doi.org/10.1038/s41551-022-00853-x)
Additional information to provide:
- Lead:
CIN-seq allows you to capture and molecularly profile rare chromosomal instability events in live cells at scale, revealing the dynamic gene programs that drive abnormal cell division.
- Quote:
CIN-seq, a “molecular spotlight” for chaotic cell division.