IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31854-8.html
   My bibliography  Save this article

A multimodal iPSC platform for cystic fibrosis drug testing

Author

Listed:
  • Andrew Berical

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University and Boston Medical Center)

  • Rhianna E. Lee

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Junjie Lu

    (Cystic Fibrosis Foundation)

  • Mary Lou Beermann

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Jake A. Le Suer

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Aditya Mithal

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Dylan Thomas

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Nicole Ranallo

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Megan Peasley

    (Cystic Fibrosis Foundation)

  • Alex Stuffer

    (Cystic Fibrosis Foundation)

  • Katherine Bukis

    (Cystic Fibrosis Foundation)

  • Rebecca Seymour

    (Cystic Fibrosis Foundation)

  • Jan Harrington

    (Cystic Fibrosis Foundation)

  • Kevin Coote

    (Cystic Fibrosis Foundation)

  • Hillary Valley

    (Cystic Fibrosis Foundation)

  • Killian Hurley

    (Education and Research Centre, Beaumont Hospital
    Royal College of Surgeons in Ireland)

  • Paul McNally

    (RCSI University of Medicine and Health Sciences
    Children’s Health Ireland)

  • Gustavo Mostoslavsky

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • John Mahoney

    (Cystic Fibrosis Foundation)

  • Scott H. Randell

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Finn J. Hawkins

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University and Boston Medical Center)

Abstract

Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in induced pluripotent stem cell-derived airway cells. In both a 3-D spheroid assay using forskolin-induced swelling as well as planar cultures composed of polarized mucociliary airway epithelial cells, we detect genotype-specific differences in CFTR baseline function and response to CFTR modulators. These results demonstrate the potential of the human induced pluripotent stem cell platform as a research tool to study CF and in particular accelerate therapeutic development for CF caused by rare variants.

Suggested Citation

  • Andrew Berical & Rhianna E. Lee & Junjie Lu & Mary Lou Beermann & Jake A. Le Suer & Aditya Mithal & Dylan Thomas & Nicole Ranallo & Megan Peasley & Alex Stuffer & Katherine Bukis & Rebecca Seymour & J, 2022. "A multimodal iPSC platform for cystic fibrosis drug testing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31854-8
    DOI: 10.1038/s41467-022-31854-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31854-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31854-8?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. Aditya Mithal & Amalia Capilla & Dar Heinze & Andrew Berical & Carlos Villacorta-Martin & Marall Vedaie & Anjali Jacob & Kristine Abo & Aleksander Szymaniak & Megan Peasley & Alexander Stuffer & John , 2020. "Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Lindsey W. Plasschaert & Rapolas Žilionis & Rayman Choo-Wing & Virginia Savova & Judith Knehr & Guglielmo Roma & Allon M. Klein & Aron B. Jaffe, 2018. "A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte," Nature, Nature, vol. 560(7718), pages 377-381, August.
    3. Daniel T. Montoro & Adam L. Haber & Moshe Biton & Vladimir Vinarsky & Brian Lin & Susan E. Birket & Feng Yuan & Sijia Chen & Hui Min Leung & Jorge Villoria & Noga Rogel & Grace Burgin & Alexander M. T, 2018. "A revised airway epithelial hierarchy includes CFTR-expressing ionocytes," Nature, Nature, vol. 560(7718), pages 319-324, August.
    Full references (including those not matched with items on IDEAS)

    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. Yunpei Xu & Shaokai Wang & Qilong Feng & Jiazhi Xia & Yaohang Li & Hong-Dong Li & Jianxin Wang, 2024. "scCAD: Cluster decomposition-based anomaly detection for rare cell identification in single-cell expression data," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Leila R. Martins & Lina Sieverling & Michelle Michelhans & Chiara Schiller & Cihan Erkut & Thomas G. P. Grünewald & Sergio Triana & Stefan Fröhling & Lars Velten & Hanno Glimm & Claudia Scholl, 2024. "Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Tim Flerlage & Jeremy Chase Crawford & E. Kaitlynn Allen & Danielle Severns & Shaoyuan Tan & Sherri Surman & Granger Ridout & Tanya Novak & Adrienne Randolph & Alina N. West & Paul G. Thomas, 2023. "Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Yuanyuan Chen & Reka Toth & Sara Chocarro & Dieter Weichenhan & Joschka Hey & Pavlo Lutsik & Stefan Sawall & Georgios T. Stathopoulos & Christoph Plass & Rocio Sotillo, 2022. "Club cells employ regeneration mechanisms during lung tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Katarina Kulhankova & Soumba Traore & Xue Cheng & Hadrien Benk-Fortin & Stéphanie Hallée & Mario Harvey & Joannie Roberge & Frédéric Couture & Sajeev Kohli & Thomas J. Gross & David K. Meyerholz & Gar, 2023. "Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Yuan Guan & Annika Enejder & Meiyue Wang & Zhuoqing Fang & Lu Cui & Shih-Yu Chen & Jingxiao Wang & Yalun Tan & Manhong Wu & Xinyu Chen & Patrik K. Johansson & Issra Osman & Koshi Kunimoto & Pierre Rus, 2021. "A human multi-lineage hepatic organoid model for liver fibrosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Zhoufeng Wang & Zhe Li & Kun Zhou & Chengdi Wang & Lili Jiang & Li Zhang & Ying Yang & Wenxin Luo & Wenliang Qiao & Gang Wang & Yinyun Ni & Shuiping Dai & Tingting Guo & Guiyi Ji & Minjie Xu & Yiying , 2021. "Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    8. Qizhou Lian & Kui Zhang & Zhao Zhang & Fuyu Duan & Liyan Guo & Weiren Luo & Bobo Wing-Yee Mok & Abhimanyu Thakur & Xiaoshan Ke & Pedram Motallebnejad & Vlad Nicolaescu & Jonathan Chen & Chui Yan Ma & , 2022. "Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Quinn T. Easter & Bruno Fernandes Matuck & Germán Beldorati Stark & Catherine L. Worth & Alexander V. Predeus & Brayon Fremin & Khoa Huynh & Vaishnavi Ranganathan & Zhi Ren & Diana Pereira & Brittany , 2024. "Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Taghreed Hirz & Shenglin Mei & Hirak Sarkar & Youmna Kfoury & Shulin Wu & Bronte M. Verhoeven & Alexander O. Subtelny & Dimitar V. Zlatev & Matthew W. Wszolek & Keyan Salari & Evan Murray & Fei Chen &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. 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.
    12. Lei Xiong & Kang Tian & Yuzhe Li & Weixi Ning & Xin Gao & Qiangfeng Cliff Zhang, 2022. "Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space," 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_s41467-022-31854-8. 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.