IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29358-6.html
   My bibliography  Save this article

A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response

Author

Listed:
  • G. Gambardella

    (Telethon Institute of Genetics and Medicine
    University of Naples Federico II, Department of Chemical, Materials and Industrial Engineering)

  • G. Viscido

    (Telethon Institute of Genetics and Medicine
    University of Naples Federico II, Department of Chemical, Materials and Industrial Engineering)

  • B. Tumaini

    (Telethon Institute of Genetics and Medicine)

  • A. Isacchi

    (NMSsrl, Nerviano Medical Sciences)

  • R. Bosotti

    (NMSsrl, Nerviano Medical Sciences)

  • D. di Bernardo

    (Telethon Institute of Genetics and Medicine
    University of Naples Federico II, Department of Chemical, Materials and Industrial Engineering)

Abstract

Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single cell atlas. We find high degree of heterogeneity in the expression of biomarkers. We then train a deconvolution algorithm on the atlas to determine cell line composition from bulk gene expression profiles of tumour biopsies, thus enabling cell line-based patient stratification. Finally, we link results from large-scale in vitro drug screening in cell lines to the single cell data to computationally predict drug responses starting from single-cell profiles. We find that transcriptional heterogeneity enables cells with differential drug sensitivity to co-exist in the same population. Our work provides a framework to determine tumour heterogeneity in terms of cell line composition and drug response.

Suggested Citation

  • G. Gambardella & G. Viscido & B. Tumaini & A. Isacchi & R. Bosotti & D. di Bernardo, 2022. "A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29358-6
    DOI: 10.1038/s41467-022-29358-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29358-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29358-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J.Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Red, 2012. "Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 492(7428), pages 290-290, December.
    2. Sydney M. Shaffer & Margaret C. Dunagin & Stefan R. Torborg & Eduardo A. Torre & Benjamin Emert & Clemens Krepler & Marilda Beqiri & Katrin Sproesser & Patricia A. Brafford & Min Xiao & Elliott Eggan , 2017. "Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance," Nature, Nature, vol. 546(7658), pages 431-435, June.
    3. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J. Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Re, 2012. "The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 483(7391), pages 603-607, March.
    4. Ke Liu & Patrick A. Newbury & Benjamin S. Glicksberg & William Z. D. Zeng & Shreya Paithankar & Eran R. Andrechek & Bin Chen, 2019. "Evaluating cell lines as models for metastatic breast cancer through integrative analysis of genomic data," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    5. Mathew J. Garnett & Elena J. Edelman & Sonja J. Heidorn & Chris D. Greenman & Anahita Dastur & King Wai Lau & Patricia Greninger & I. Richard Thompson & Xi Luo & Jorge Soares & Qingsong Liu & Francesc, 2012. "Systematic identification of genomic markers of drug sensitivity in cancer cells," Nature, Nature, vol. 483(7391), pages 570-575, March.
    6. Charles M. Perou & Therese Sørlie & Michael B. Eisen & Matt van de Rijn & Stefanie S. Jeffrey & Christian A. Rees & Jonathan R. Pollack & Douglas T. Ross & Hilde Johnsen & Lars A. Akslen & Øystein Flu, 2000. "Molecular portraits of human breast tumours," Nature, Nature, vol. 406(6797), pages 747-752, August.
    7. Mihriban Karaayvaz & Simona Cristea & Shawn M. Gillespie & Anoop P. Patel & Ravindra Mylvaganam & Christina C. Luo & Michelle C. Specht & Bradley E. Bernstein & Franziska Michor & Leif W. Ellisen, 2018. "Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    8. Nicole Vincent Jordan & Aditya Bardia & Ben S. Wittner & Cyril Benes & Matteo Ligorio & Yu Zheng & Min Yu & Tilak K. Sundaresan & Joseph A. Licausi & Rushil Desai & Ryan M. O’Keefe & Richard Y. Ebrigh, 2016. "HER2 expression identifies dynamic functional states within circulating breast cancer cells," Nature, Nature, vol. 537(7618), pages 102-106, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Michael J. Geuenich & Dae-won Gong & Kieran R. Campbell, 2024. "The impacts of active and self-supervised learning on efficient annotation of single-cell expression data," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Shaojie Qin & Yi Zhang & Mingying Shi & Daiyu Miao & Jiansen Lu & Lu Wen & Yu Bai, 2024. "In-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zheqi Li & Olivia McGinn & Yang Wu & Amir Bahreini & Nolan M. Priedigkeit & Kai Ding & Sayali Onkar & Caleb Lampenfeld & Carol A. Sartorius & Lori Miller & Margaret Rosenzweig & Ofir Cohen & Nikhil Wa, 2022. "ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Caitlin E. Mills & Kartik Subramanian & Marc Hafner & Mario Niepel & Luca Gerosa & Mirra Chung & Chiara Victor & Benjamin Gaudio & Clarence Yapp & Ajit J. Nirmal & Nicholas Clark & Peter K. Sorger, 2022. "Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Shi, Chengchun & Xu, Tianlin & Bergsma, Wicher & Li, Lexin, 2021. "Double generative adversarial networks for conditional independence testing," LSE Research Online Documents on Economics 112550, London School of Economics and Political Science, LSE Library.
    4. Min Pan & William C. Wright & Richard H. Chapple & Asif Zubair & Manbir Sandhu & Jake E. Batchelder & Brandt C. Huddle & Jonathan Low & Kaley B. Blankenship & Yingzhe Wang & Brittney Gordon & Payton A, 2021. "The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    5. Hyeong-Min Lee & William C. Wright & Min Pan & Jonathan Low & Duane Currier & Jie Fang & Shivendra Singh & Stephanie Nance & Ian Delahunty & Yuna Kim & Richard H. Chapple & Yinwen Zhang & Xueying Liu , 2023. "A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Jurica Levatić & Marina Salvadores & Francisco Fuster-Tormo & Fran Supek, 2022. "Mutational signatures are markers of drug sensitivity of cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. Zhaoxiang Cai & Sofia Apolinário & Ana R. Baião & Clare Pacini & Miguel D. Sousa & Susana Vinga & Roger R. Reddel & Phillip J. Robinson & Mathew J. Garnett & Qing Zhong & Emanuel Gonçalves, 2024. "Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Han Jin & Cheng Zhang & Martin Zwahlen & Kalle Feilitzen & Max Karlsson & Mengnan Shi & Meng Yuan & Xiya Song & Xiangyu Li & Hong Yang & Hasan Turkez & Linn Fagerberg & Mathias Uhlén & Adil Mardinoglu, 2023. "Systematic transcriptional analysis of human cell lines for gene expression landscape and tumor representation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Seungyeul Yoo & Abhilasha Sinha & Dawei Yang & Nasser K. Altorki & Radhika Tandon & Wenhui Wang & Deebly Chavez & Eunjee Lee & Ayushi S. Patel & Takashi Sato & Ranran Kong & Bisen Ding & Eric E. Schad, 2022. "Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Alon Stern & Mariam Fokra & Boris Sarvin & Ahmad Abed Alrahem & Won Dong Lee & Elina Aizenshtein & Nikita Sarvin & Tomer Shlomi, 2023. "Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    12. Sayantani Ghosh Dastidar & Bony Kumar & Bo Lauckner & Damien Parrello & Danielle Perley & Maria Vlasenok & Antariksh Tyagi & Nii Koney-Kwaku Koney & Ata Abbas & Sergei Nechaev, 2023. "Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Cemal Erdem & Sean M. Gross & Laura M. Heiser & Marc R. Birtwistle, 2023. "MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Lisa Veghini & Davide Pasini & Rui Fang & Pietro Delfino & Dea Filippini & Christian Neander & Caterina Vicentini & Elena Fiorini & Francesca Lupo & Sabrina L. D’Agosto & Carmine Carbone & Antonio Ago, 2024. "Differential activity of MAPK signalling defines fibroblast subtypes in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Felicity J. Ashcroft & Asimina Bourboula & Nur Mahammad & Efrosini Barbayianni & Astrid J. Feuerherm & Thanh Thuy Nguyen & Daiki Hayashi & Maroula G. Kokotou & Konstantinos Alevizopoulos & Edward A. D, 2025. "Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A2 α for targeted cancer therapy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    17. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    18. Souleymane Abdoul-Azize & Rihab Hami & Gaetan Riou & Céline Derambure & Camille Charbonnier & Jean-Pierre Vannier & Monica L. Guzman & Pascale Schneider & Olivier Boyer, 2024. "Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    19. Michael Kugler & Felix J. Metzner & Gregor Witte & Karl-Peter Hopfner & Katja Lammens, 2024. "Phosphorylation-mediated conformational change regulates human SLFN11," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Philip East & Gavin P. Kelly & Dhruva Biswas & Michela Marani & David C. Hancock & Todd Creasy & Kris Sachsenmeier & Charles Swanton & Julian Downward & Sophie de Carné Trécesson, 2022. "RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29358-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.