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Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung

Author

Listed:
  • Daniel Lafkas

    (Genentech, Inc.)

  • Amy Shelton

    (Genentech, Inc.)

  • Cecilia Chiu

    (Genentech, Inc.)

  • Gladys de Leon Boenig

    (Genentech, Inc.)

  • Yongmei Chen

    (Genentech, Inc.)

  • Scott S. Stawicki

    (Genentech, Inc.)

  • Christian Siltanen

    (Genentech, Inc.
    Present addresses: Department of Biomedical Engineering, University of California, Davis, 451 E. Health Sciences Drive, Davis, California 95616, USA (C.S.); Amgen, Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA (J.E.).)

  • Mike Reichelt

    (Genentech, Inc.)

  • Meijuan Zhou

    (Genentech, Inc.)

  • Xiumin Wu

    (Genentech, Inc.)

  • Jeffrey Eastham-Anderson

    (Genentech, Inc.)

  • Heather Moore

    (Genentech, Inc.)

  • Meron Roose-Girma

    (Genentech, Inc.)

  • Yvonne Chinn

    (Genentech, Inc.)

  • Julie Q. Hang

    (Genentech, Inc.)

  • Søren Warming

    (Genentech, Inc.)

  • Jackson Egen

    (Genentech, Inc.
    Present addresses: Department of Biomedical Engineering, University of California, Davis, 451 E. Health Sciences Drive, Davis, California 95616, USA (C.S.); Amgen, Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA (J.E.).)

  • Wyne P. Lee

    (Genentech, Inc.)

  • Cary Austin

    (Genentech, Inc.)

  • Yan Wu

    (Genentech, Inc.)

  • Jian Payandeh

    (Genentech, Inc.)

  • John B. Lowe

    (Genentech, Inc.)

  • Christian W. Siebel

    (Genentech, Inc.)

Abstract

Inhibitory antibodies to two specific human and mouse Notch ligands, Jagged1 and Jagged2, are generated and shown to have beneficial effects in a goblet cell metaplasia asthma model; systemic Jagged1 inhibition transdifferentiates secretory cells into ciliated cells in the mouse, demonstrating that Jagged1 from ciliated cells normally holds back secretory cells to adopt the ciliated fate.

Suggested Citation

  • Daniel Lafkas & Amy Shelton & Cecilia Chiu & Gladys de Leon Boenig & Yongmei Chen & Scott S. Stawicki & Christian Siltanen & Mike Reichelt & Meijuan Zhou & Xiumin Wu & Jeffrey Eastham-Anderson & Heath, 2015. "Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung," Nature, Nature, vol. 528(7580), pages 127-131, December.
    • Handle: RePEc:nat:nature:v:528:y:2015:i:7580:d:10.1038_nature15715
    DOI: 10.1038/nature15715
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    Citations

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    Cited by:

    1. Songbai Zhang & Ayako Miyakawa & Malin Wickström & Cecilia Dyberg & Lauri Louhivuori & Manuel Varas-Godoy & Kati Kemppainen & Shigeaki Kanatani & Dagmara Kaczynska & Ivar Dehnisch Ellström & Lotta Elf, 2022. "GIT1 protects against breast cancer growth through negative regulation of Notch," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Torleif Tollefsrud Gjølberg & Jonas Aakre Wik & Hanna Johannessen & Stig Krüger & Nicola Bassi & Panagiotis F. Christopoulos & Malin Bern & Stian Foss & Goran Petrovski & Morten C. Moe & Guttorm Haral, 2023. "Antibody blockade of Jagged1 attenuates choroidal neovascularization," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Mayra Cruz Tleugabulova & Sandra P. Melo & Aaron Wong & Alexander Arlantico & Meizi Liu & Joshua D. Webster & Julia Lau & Antonie Lechner & Basak Corak & Jonathan J. Hodgins & Venkata S. Garlapati & M, 2024. "Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Douglas G. Brownfield & Alex Diaz Arce & Elisa Ghelfi & Astrid Gillich & Tushar J. Desai & Mark A. Krasnow, 2022. "Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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