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5 results on '"Weselak, J."'

1. Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Author

Kuett, Laura, Catena, Raúl, Özcan, Alaz, Plüss, Alex, Ali, H. R., Sa’d, M. Al, Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Yoldaş, A. Küpcü, Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, I., O’Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Xia, C., Zheng, P., Zhuang, X., Schraml, Peter, Moch, Holger, de Souza, Natalie, and Bodenmiller, Bernd

Subjects
Cancer Research, Oncology
Abstract

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

Published
2021
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2. Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Author

Kuett, L, Catena, R, ��zcan, A, Pl��ss, A, Ali, HR, Sa���d, MA, Alon, S, Aparicio, S, Battistoni, G, Balasubramanian, Shankar, Becker, R, Bodenmiller, B, Boyden, ES, Bressan, D, Bruna, A, Burger, M, Caldas, Carlos, Callari, M, Cannell, IG, Casbolt, H, Chornay, N, Cui, Y, Dariush, Aliakbar, Dinh, K, Emenari, A, Eyal-Lubling, Y, Fan, J, Fatemi, A, Fisher, E, Gonz��lez-Solares, EA, Gonz��lez-Fern��ndez, C, Goodwin, D, Greenwood, W, Grimaldi, F, Hannon, GJ, Harris, S, Jauset, C, Joyce, JA, Karagiannis, ED, Kova��evi��, T, Kunes, R, Yolda��, AK, Lai, D, Laks, E, Lee, H, Lee, M, Lerda, G, Li, Y, McPherson, A, Millar, N, Mulvey, CM, Nugent, I, O���Flanagan, CH, Paez-Ribes, M, Pearsall, I, Qosaj, F, Roth, AJ, Rueda, OM, Ruiz, T, Sawicka, K, Sep��lveda, LA, Shah, SP, Shea, A, Sinha, A, Smith, A, Tavar��, S, Tietscher, S, V��zquez-Garc��a, I, Vogl, SL, Walton, NA, Wassie, AT, Watson, SS, Weselak, J, Wild, SA, Williams, E, Windhager, J, Xia, C, Zheng, P, Zhuang, X, Schraml, P, Moch, H, De Souza, N, Ali, Raza [0000-0001-7587-0906], Balasubramanian, Shankar [0000-0002-0281-5815], Caldas, Carlos [0000-0003-3547-1489], Hannon, Gregory [0000-0003-4021-3898], Walton, Nicholas [0000-0003-3983-8778], and Apollo - University of Cambridge Repository

Subjects
Imaging, Three-Dimensional, Tumor Microenvironment, Humans, Breast Neoplasms, Female, Antibodies, Image Cytometry
Abstract

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

Published
2022

3. Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response

Author

Georgopoulou, Dimitra, Callari, Maurizio, Rueda, Oscar M., Shea, Abigail, Martin, Alistair, Giovannetti, Agnese, Qosaj, Fatime, Dariush, Ali, Chin, Suet-Feung, Carnevalli, Larissa S., Provenzano, Elena, Greenwood, Wendy, Lerda, Giulia, Esmaeilishirazifard, Elham, O’Reilly, Martin, Serra, Violeta, Bressan, Dario, Mills, Gordon B., Ali, H. Raza, Cosulich, Sabina S., Hannon, Gregory J., Bruna, Alejandra, Caldas, Carlos, Ali, H. R., Al Sa’d, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, O., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Küpcü, Yoldaş A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, F., O’Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., Zhuang, X., Rueda, Oscar M. [0000-0003-0008-4884], Giovannetti, Agnese [0000-0001-5207-7243], Chin, Suet-Feung [0000-0001-5697-1082], Carnevalli, Larissa S. [0000-0001-7432-0195], Provenzano, Elena [0000-0003-3345-3965], Serra, Violeta [0000-0001-6620-1065], Bressan, Dario [0000-0003-3592-699X], Mills, Gordon B. [0000-0002-0144-9614], Ali, H. Raza [0000-0001-7587-0906], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository

Subjects
13/1, 13/105, article, 13/106, 38/39, 45/23, 631/67/1347, 631/67/2329
Abstract

Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, Funder: AstraZeneca; doi: https://doi.org/10.13039/100004325, The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.

Published
2021
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4. Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems

Author

Alon, Shahar, Goodwin, Daniel R., Sinha, Anubhav, Wassie, Asmamaw T., Chen, Fei, Daugharthy, Evan R., Bando, Yosuke, Kajita, Atsushi, Xue, Andrew G., Marrett, Karl, Prior, Robert, Cui, Yi, Payne, Andrew C., Yao, Chun-Chen, Suk, Ho-Jun, Wang, Ru, Yu, Chih-Chieh (Jay), Tillberg, Paul, Reginato, Paul, Pak, Nikita, Liu, Songlei, Punthambaker, Sukanya, Iyer, Eswar P. R., Kohman, Richie E., Miller, Jeremy A., Lein, Ed S., Lako, Ana, Cullen, Nicole, Rodig, Scott, Helvie, Karla, Abravanel, Daniel L., Wagle, Nikhil, Johnson, Bruce E., Klughammer, Johanna, Slyper, Michal, Waldman, Julia, Jané-Valbuena, Judit, Rozenblatt-Rosen, Orit, Regev, Aviv, Church, George M., Marblestone, Adam H., Boyden, Edward S., Ali, H. R., Al Sa’d, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E. S., Bressan, D., Bruna, A., Burger, Marcel, Caldas, C., Callari, M., Cannell, I. G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E. A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G. J., Harris, O., Harris, S., Jauset, C., Joyce, J. A., Karagiannis, E. D., Kovačević, T., Kuett, L., Kunes, R., Küpcü Yoldaş, A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C. M., Nugent, F., O'Flanagan, C. H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A. J., Rueda, O. M., Ruiz, T., Sawicka, K., Sepúlveda, L. A., Shah, S. P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S. L., Walton, N. A., Wassie, A. T., Watson, S. S., Weselak, J., Wild, S. A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., and Zhuang, X.

Subjects
In situ, Cell type, Dendritic spine, Sequence analysis, Dendritic Spines, Breast Neoplasms, Computational biology, Biology, Biochemistry, Article, Transcriptome, Mice, 03 medical and health sciences, Animals, Humans, splice, Molecular Biology, Gene, Visual Cortex, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Sequence Analysis, RNA, Gene Expression Profiling, Computational Biology, RNA, Cell Biology, Molecular Imaging, Female, Single-Cell Analysis, Biotechnology
Abstract

Identifying transcript location in cells Identifying where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy has allowed for better visualization of small structures by expanding the tissues with a polymer- and hydrogel-based system. Alon et al. combined expansion microscopy with long-read in situ RNA sequencing, resulting in a more precise visualization of the location of specific transcripts. This method, termed “ExSeq” for expansion sequencing, was used to detect RNAs, both new transcripts and those previously demonstrated to localize to neuronal dendrites. Unlike other in situ sequencing methods, ExSeq does not target sets of genes. This technology thus unites spatial resolution, multiplexing, and an unbiased approach to reveal insights into RNA localization and its physiological roles in developing and active tissue. Science , this issue p. eaax2656

Published
2021

5. Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response

Author

Sabina S Cosulich, Abigail Shea, Maurizio Callari, A. Dariush, Elena Provenzano, Martin O'Reilly, Carlos Caldas, Dimitra Georgopoulou, Agnese Giovannetti, Oscar M. Rueda, Gregory J. Hannon, Suet-Feung Chin, Giulia Lerda, Elham Esmaeilishirazifard, Alistair Martin, Violeta Serra, Fatime Qosaj, Wendy Greenwood, Dario Bressan, Larissa S. Carnevalli, Alejandra Bruna, H. Raza Ali, Gordon B. Mills, Rueda, Oscar M [0000-0003-0008-4884], Giovannetti, Agnese [0000-0001-5207-7243], Chin, Suet-Feung [0000-0001-5697-1082], Carnevalli, Larissa S [0000-0001-7432-0195], Provenzano, Elena [0000-0003-3345-3965], Serra, Violeta [0000-0001-6620-1065], Bressan, Dario [0000-0003-3592-699X], Mills, Gordon B [0000-0002-0144-9614], Ali, H Raza [0000-0001-7587-0906], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository, IMAXT Consortium, Ali, H.R., Al Sa'd, M., Alon, S., Aparicio, S., Battistoni, G., Balasubramanian, S., Becker, R., Bodenmiller, B., Boyden, E.S., Bressan, D., Bruna, A., Burger, M., Caldas, C., Callari, M., Cannell, I.G., Casbolt, H., Chornay, N., Cui, Y., Dariush, A., Dinh, K., Emenari, A., Eyal-Lubling, Y., Fan, J., Fatemi, A., Fisher, E., González-Solares, E.A., González-Fernández, C., Goodwin, D., Greenwood, W., Grimaldi, F., Hannon, G.J., Harris, O., Harris, S., Jauset, C., Joyce, J.A., Karagiannis, E.D., Kovačević, T., Kuett, L., Kunes, R., Küpcü, Y.A., Lai, D., Laks, E., Lee, H., Lee, M., Lerda, G., Li, Y., McPherson, A., Millar, N., Mulvey, C.M., Nugent, F., O'Flanagan, C.H., Paez-Ribes, M., Pearsall, I., Qosaj, F., Roth, A.J., Rueda, O.M., Ruiz, T., Sawicka, K., Sepúlveda, L.A., Shah, S.P., Shea, A., Sinha, A., Smith, A., Tavaré, S., Tietscher, S., Vázquez-García, I., Vogl, S.L., Walton, N.A., Wassie, A.T., Watson, S.S., Weselak, J., Wild, S.A., Williams, E., Windhager, J., Whitmarsh, T., Xia, C., Zheng, P., and Zhuang, X.

Subjects
0301 basic medicine, Pyridines, Science, Tumour heterogeneity, Morpholines, Cell, General Physics and Astronomy, Breast Neoplasms, Drug resistance, Mice, SCID, Biology, Animals, Benzamides/pharmacology, Breast Neoplasms/drug therapy, Breast Neoplasms/genetics, Breast Neoplasms/metabolism, Cell Line, Tumor, Drug Resistance, Neoplasm/drug effects, Drug Resistance, Neoplasm/genetics, Female, Heterografts/drug effects, Heterografts/metabolism, Humans, MCF-7 Cells, Mice, Inbred NOD, Mice, Knockout, Morpholines/pharmacology, Piperazines/pharmacology, Protein Kinase Inhibitors/pharmacology, Pyridines/pharmacology, Pyrimidines/pharmacology, Treatment Outcome, Xenograft Model Antitumor Assays/methods, General Biochemistry, Genetics and Molecular Biology, Article, Piperazines, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Mass cytometry, Protein Kinase Inhibitors, Multidisciplinary, Genetic heterogeneity, Cancer, General Chemistry, medicine.disease, Biobank, Phenotype, Xenograft Model Antitumor Assays, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Pyrimidines, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Benzamides, Cancer research, Heterografts
Abstract

The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance., The heterogeneity of breast cancer has a major role in drug response and resistance. In this study, the authors use patient-derived tumour xenografts as a platform for drug testing and correlation with single-cell proteomic phenotypes characterized by mass cytometry.

Published
2021
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