IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v507y2014i7491d10.1038_nature12930.html
   My bibliography  Save this article

Alveolar progenitor and stem cells in lung development, renewal and cancer

Author

Listed:
  • Tushar J. Desai

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Douglas G. Brownfield

    (Stanford University School of Medicine)

  • Mark A. Krasnow

    (Stanford University School of Medicine)

Abstract

Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.

Suggested Citation

  • Tushar J. Desai & Douglas G. Brownfield & Mark A. Krasnow, 2014. "Alveolar progenitor and stem cells in lung development, renewal and cancer," Nature, Nature, vol. 507(7491), pages 190-194, March.
  • Handle: RePEc:nat:nature:v:507:y:2014:i:7491:d:10.1038_nature12930
    DOI: 10.1038/nature12930
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature12930
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature12930?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. 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.
    2. Kuei-Pin Chung & Chih-Ning Cheng & Yi-Jung Chen & Chia-Lang Hsu & Yen-Lin Huang & Min-Shu Hsieh & Han-Chun Kuo & Ya-Ting Lin & Yi-Hsiu Juan & Kiichi Nakahira & Yen-Fu Chen & Wei-Lun Liu & Sheng-Yuan R, 2024. "Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Dalia Hassan & Jichao Chen, 2024. "CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Maik Pietzner & Robert Lorenz Chua & Eleanor Wheeler & Katharina Jechow & Julian D. S. Willett & Helena Radbruch & Saskia Trump & Bettina Heidecker & Hugo Zeberg & Frank L. Heppner & Roland Eils & Mar, 2022. "ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. 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.
    6. Ning Yang & Joseph M. Luna & Peihong Dai & Yi Wang & Charles M. Rice & Liang Deng, 2022. "Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Christopher W. Murray & Jennifer J. Brady & Mingqi Han & Hongchen Cai & Min K. Tsai & Sarah E. Pierce & Ran Cheng & Janos Demeter & David M. Feldser & Peter K. Jackson & David B. Shackelford & Monte M, 2022. "LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    8. Benjamin Ng & Kevin Y. Huang & Chee Jian Pua & Sivakumar Viswanathan & Wei-Wen Lim & Fathima F. Kuthubudeen & Yu-Ning Liu & An An Hii & Benjamin L. George & Anissa A. Widjaja & Enrico Petretto & Stuar, 2024. "Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. 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.
    10. Xin Pan & Lan Wang & Juntang Yang & Yingge Li & Min Xu & Chenxi Liang & Lulu Liu & Zhongzheng Li & Cong Xia & Jiaojiao Pang & Mengyuan Wang & Meng Li & Saiya Guo & Peishuo Yan & Chen Ding & Ivan O. Ro, 2024. "TRĪ² activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA," Nature Communications, Nature, vol. 15(1), pages 1-19, 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:nature:v:507:y:2014:i:7491:d:10.1038_nature12930. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.