PCLAF-DREAM drives alveolar cell plasticity for lung regeneration

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 Chen, Carla Kim and Jae-Il Park ()
Additional contact information
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

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53330-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53330-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53330-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().