IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53330-1.html
   My bibliography  Save this article

PCLAF-DREAM drives alveolar cell plasticity for lung regeneration

Author

Listed:
  • Bongjun Kim

    (The University of Texas MD Anderson Cancer Center)

  • Yuanjian Huang

    (The University of Texas MD Anderson Cancer Center)

  • Kyung-Pil Ko

    (The University of Texas MD Anderson Cancer Center)

  • Shengzhe Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Gengyi Zou

    (The University of Texas MD Anderson Cancer Center)

  • Jie Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Moon Jong Kim

    (The University of Texas MD Anderson Cancer Center)

  • Danielle Little

    (The University of Texas MD Anderson Cancer Center)

  • Lisandra Vila Ellis

    (The University of Texas MD Anderson Cancer Center)

  • Margherita Paschini

    (Boston Children’s Hospital)

  • Sohee Jun

    (The University of Texas MD Anderson Cancer Center)

  • Kwon-Sik Park

    (University of Virginia)

  • Jichao Chen

    (The University of Texas MD Anderson Cancer Center)

  • Carla Kim

    (Boston Children’s Hospital)

  • Jae-Il Park

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Cell plasticity, changes in cell fate, is crucial for tissue regeneration. In the lung, failure of regeneration leads to diseases, including fibrosis. However, the mechanisms governing alveolar cell plasticity during lung repair remain elusive. We previously showed that PCLAF remodels the DREAM complex, shifting the balance from cell quiescence towards cell proliferation. Here, we find that PCLAF expression is specific to proliferating lung progenitor cells, along with the DREAM target genes transactivated by lung injury. Genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. Mechanistically, the PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation, which promotes AT1 cell generation from AT2 cells. Furthermore, phenelzine that mimics the PCLAF-DREAM transcriptional signature increases AT2 cell plasticity, preventing lung fibrosis in organoids and mice. Our study reveals the unexpected role of the PCLAF-DREAM axis in promoting alveolar cell plasticity, beyond cell proliferation control, proposing a potential therapeutic avenue for lung fibrosis prevention.

Suggested Citation

  • Bongjun Kim & Yuanjian Huang & Kyung-Pil Ko & Shengzhe Zhang & Gengyi Zou & Jie Zhang & Moon Jong Kim & Danielle Little & Lisandra Vila Ellis & Margherita Paschini & Sohee Jun & Kwon-Sik Park & Jichao, 2024. "PCLAF-DREAM drives alveolar cell plasticity for lung regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53330-1
    DOI: 10.1038/s41467-024-53330-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53330-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-53330-1?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. Xin Wang & Youn-Sang Jung & Sohee Jun & Sunhye Lee & Wenqi Wang & Andrea Schneider & Young Sun Oh & Steven H. Lin & Bum-Joon Park & Junjie Chen & Khandan Keyomarsi & Jae-Il Park, 2016. "PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    2. SeungHye Han & Minho Lee & Youngjin Shin & Regina Giovanni & Ram P. Chakrabarty & Mariana M. Herrerias & Laura A. Dada & Annette S. Flozak & Paul A. Reyfman & Basil Khuder & Colleen R. Reczek & Lin Ga, 2023. "Mitochondrial integrated stress response controls lung epithelial cell fate," Nature, Nature, vol. 620(7975), pages 890-897, August.
    3. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    4. Maximilian Strunz & Lukas M. Simon & Meshal Ansari & Jaymin J. Kathiriya & Ilias Angelidis & Christoph H. Mayr & George Tsidiridis & Marius Lange & Laura F. Mattner & Min Yee & Paulina Ogar & Arunima , 2020. "Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    5. Danielle R. Little & Anne M. Lynch & Yun Yan & Haruhiko Akiyama & Shioko Kimura & Jichao Chen, 2021. "Differential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    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. 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.
    2. 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.
    3. Andrea Toth & Paranthaman Kannan & John Snowball & Matthew Kofron & Joseph A. Wayman & James P. Bridges & Emily R. Miraldi & Daniel Swarr & William J. Zacharias, 2023. "Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Lucy Xia & Christy Lee & Jingyi Jessica Li, 2024. "Statistical method scDEED for detecting dubious 2D single-cell embeddings and optimizing t-SNE and UMAP hyperparameters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    5. 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.
    6. 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.
    7. Huanhuan Tan & Weixu Wang & Congjin Zhou & Yanfeng Wang & Shu Zhang & Pinglan Yang & Rui Guo & Wei Chen & Jinwen Zhang & Lan Ye & Yiqiang Cui & Ting Ni & Ke Zheng, 2023. "Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    9. Christoph Ziegenhain & Rickard Sandberg, 2021. "BAMboozle removes genetic variation from human sequence data for open data sharing," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    10. Yoshiaki Yasumizu & Naganari Ohkura & Hisashi Murata & Makoto Kinoshita & Soichiro Funaki & Satoshi Nojima & Kansuke Kido & Masaharu Kohara & Daisuke Motooka & Daisuke Okuzaki & Shuji Suganami & Eriko, 2022. "Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    12. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    13. Lin Yang & Qiongliang Liu & Pramod Kumar & Arunima Sengupta & Ali Farnoud & Ruolin Shen & Darya Trofimova & Sebastian Ziegler & Neda Davoudi & Ali Doryab & Ali Önder Yildirim & Markus E. Diefenbacher , 2024. "LungVis 1.0: an automatic AI-powered 3D imaging ecosystem unveils spatial profiling of nanoparticle delivery and acinar migration of lung macrophages," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    14. Rinako Nakagawa & Miriam Llorian & Sunita Varsani-Brown & Probir Chakravarty & Jeannie M. Camarillo & David Barry & Roger George & Neil P. Blackledge & Graham Duddy & Neil L. Kelleher & Robert J. Klos, 2024. "Epi-microRNA mediated metabolic reprogramming counteracts hypoxia to preserve affinity maturation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. David J. Dittmar & Franziska Pielmeier & Nicholas Strieder & Alexander Fischer & Michael Herbst & Hanna Stanewsky & Niklas Wenzl & Eveline Röseler & Rüdiger Eder & Claudia Gebhard & Lucia Schwarzfisch, 2024. "Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Seong Eun Lee & Seongyeol Park & Shinae Yi & Na Rae Choi & Mi Ae Lim & Jae Won Chang & Ho-Ryun Won & Je Ryong Kim & Hye Mi Ko & Eun-Jae Chung & Young Joo Park & Sun Wook Cho & Hyeong Won Yu & June You, 2024. "Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. David G. Priest & Takeshi Ebihara & Janyerkye Tulyeu & Jonas N. Søndergaard & Shuhei Sakakibara & Fuminori Sugihara & Shunichiro Nakao & Yuki Togami & Jumpei Yoshimura & Hiroshi Ito & Shinya Onishi & , 2024. "Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    20. Jeff Yat-Fai Chung & Philip Chiu-Tsun Tang & Max Kam-Kwan Chan & Vivian Weiwen Xue & Xiao-Ru Huang & Calvin Sze-Hang Ng & Dongmei Zhang & Kam-Tong Leung & Chun-Kwok Wong & Tin-Lap Lee & Eric W-F Lam &, 2023. "Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma," Nature Communications, Nature, vol. 14(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:15:y:2024:i:1:d:10.1038_s41467-024-53330-1. 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.