IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34763-y.html
   My bibliography  Save this article

mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity

Author

Listed:
  • Kuan Zhang

    (University of California)

  • Erica Yao

    (University of California)

  • Ethan Chuang

    (University of California)

  • Biao Chen

    (University of California)

  • Evelyn Y. Chuang

    (University of California)

  • Pao-Tien Chuang

    (University of California)

Abstract

Formation of branched organs requires sequential differentiation of stem cells. In this work, we find that the conducting airways derived from SOX2+ progenitors in the murine lungs fail to form without mTOR complex 1 (mTORC1) signaling and are replaced by lung cysts. Proximal-distal patterning through transitioning of distal SOX9+ progenitors to proximal SOX2+ cells is disrupted. Mitochondria number and ATP production are reduced. Compromised mitochondrial capacity results in a similar defect as that in mTORC1-deficient lungs. This suggests that mTORC1 promotes differentiation of SOX9+ progenitors to form the conducting airways by modulating mitochondrial capacity. Surprisingly, in all mutants, saccules are produced from lung cysts at the proper developmental time despite defective branching. SOX9+ progenitors also differentiate into alveolar epithelial type I and type II cells within saccules. These findings highlight selective utilization of energy and regulatory programs during stem cell differentiation to produce distinct structures of the mammalian lungs.

Suggested Citation

  • Kuan Zhang & Erica Yao & Ethan Chuang & Biao Chen & Evelyn Y. Chuang & Pao-Tien Chuang, 2022. "mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34763-y
    DOI: 10.1038/s41467-022-34763-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34763-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34763-y?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. Denise Martinez Alanis & Daniel R. Chang & Haruhiko Akiyama & Mark A. Krasnow & Jichao Chen, 2014. "Two nested developmental waves demarcate a compartment boundary in the mouse lung," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    2. Ross J. Metzger & Ophir D. Klein & Gail R. Martin & Mark A. Krasnow, 2008. "The branching programme of mouse lung development," Nature, Nature, vol. 453(7196), pages 745-750, June.
    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. 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.
    2. Mehmet Can Uçar & Dmitrii Kamenev & Kazunori Sunadome & Dominik Fachet & Francois Lallemend & Igor Adameyko & Saida Hadjab & Edouard Hannezo, 2021. "Theory of branching morphogenesis by local interactions and global guidance," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Yihwa Kim & Robert Sinclair & Nol Chindapol & Jaap A Kaandorp & Erik De Schutter, 2012. "Geometric Theory Predicts Bifurcations in Minimal Wiring Cost Trees in Biology Are Flat," PLOS Computational Biology, Public Library of Science, vol. 8(4), pages 1-7, April.
    4. Anna Urciuolo & Giovanni Giuseppe Giobbe & Yixiao Dong & Federica Michielin & Luca Brandolino & Michael Magnussen & Onelia Gagliano & Giulia Selmin & Valentina Scattolini & Paolo Raffa & Paola Caccin , 2023. "Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Elif Tekin & David Hunt & Mitchell G Newberry & Van M Savage, 2016. "Do Vascular Networks Branch Optimally or Randomly across Spatial Scales?," PLOS Computational Biology, Public Library of Science, vol. 12(11), pages 1-28, November.
    6. Mingzhu Sun & Hui Xu & Xingjuan Zeng & Xin Zhao, 2017. "Automated numerical simulation of biological pattern formation based on visual feedback simulation framework," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-16, February.
    7. Cemal Cagatay Bilgin & Shayoni Ray & Banu Baydil & William P Daley & Melinda Larsen & Bülent Yener, 2012. "Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-19, March.
    8. Mehmet Can Uçar & Edouard Hannezo & Emmi Tiilikainen & Inam Liaqat & Emma Jakobsson & Harri Nurmi & Kari Vaahtomeri, 2023. "Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Yina Guo & Mingzhu Sun & Alan Garfinkel & Xin Zhao, 2014. "Mechanisms of Side Branching and Tip Splitting in a Model of Branching Morphogenesis," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-14, July.

    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_s41467-022-34763-y. 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.