pheno-seq - linking morphological features to gene expression in 3D cell culture systems

Tirier SM, Park J, Preusser F, Amrhein L, Gu Z, Steiger S, Mallm J-P, Waschow M, Eismann B, Gut M, Gut IG, et al. (2018)
bioRxiv.

Preprint | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Transcriptional heterogeneity can be dissected by single-cell RNA-sequencing, but these technologies suffer from low RNA-input and fail to directly correlate gene expression with contextual cellular phenotypes. Here we present "pheno-seq" for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids derived from 3D models of breast and colorectal cancer. Specifically, we identify characteristic expression signatures that are associated with heterogeneous invasive and proliferative behavior including a rare cell subtype. Furthermore, we identify functionally relevant transcriptional regulators missed by single-cell RNA-seq, link visual phenotypes defined by heterogenous expression to inhibitor response and infer single-cell regulatory states by deconvolution. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently prove to be useful for translational research.
Erscheinungsjahr
2018
Zeitschriftentitel
bioRxiv
Page URI
https://pub.uni-bielefeld.de/record/2933887

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Tirier SM, Park J, Preusser F, et al. pheno-seq - linking morphological features to gene expression in 3D cell culture systems. bioRxiv. 2018.
Tirier, S. M., Park, J., Preusser, F., Amrhein, L., Gu, Z., Steiger, S., Mallm, J. - P., et al. (2018). pheno-seq - linking morphological features to gene expression in 3D cell culture systems. bioRxiv. doi:10.1101/311472
Tirier, S. M., Park, J., Preusser, F., Amrhein, L., Gu, Z., Steiger, S., Mallm, J. - P., Waschow, M., Eismann, B., Gut, M., et al. (2018). pheno-seq - linking morphological features to gene expression in 3D cell culture systems. bioRxiv.
Tirier, S.M., et al., 2018. pheno-seq - linking morphological features to gene expression in 3D cell culture systems. bioRxiv.
S.M. Tirier, et al., “pheno-seq - linking morphological features to gene expression in 3D cell culture systems”, bioRxiv, 2018.
Tirier, S.M., Park, J., Preusser, F., Amrhein, L., Gu, Z., Steiger, S., Mallm, J.-P., Waschow, M., Eismann, B., Gut, M., Gut, I.G., Rippe, K., Schlesner, M., Theis, F., Fuchs, C., Ball, C.R., Glimm, H., Eils, R., Conrad, C.: pheno-seq - linking morphological features to gene expression in 3D cell culture systems. bioRxiv. (2018).
Tirier, Stephan M., Park, Jeongbin, Preusser, Friedrich, Amrhein, Lisa, Gu, Zuguang, Steiger, Simon, Mallm, Jan-Philipp, Waschow, Marcel, Eismann, Bjoern, Gut, Marta, Gut, Ivo G., Rippe, Karsten, Schlesner, Matthias, Theis, Fabian, Fuchs, Christiane, Ball, Claudia R., Glimm, Hanno, Eils, Roland, and Conrad, Christian. “pheno-seq - linking morphological features to gene expression in 3D cell culture systems”. bioRxiv (2018).

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