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CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair

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  • Dalia Hassan

    (the University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences)

  • Jichao Chen

    (the University of Texas MD Anderson Cancer Center
    University of Cincinnati and Cincinnati Children’s Hospital Medical Center)

Abstract

Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity where Cebpa mutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48632-3
    DOI: 10.1038/s41467-024-48632-3
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    1. 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.
    2. 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.
    3. Barbara Treutlein & Doug G. Brownfield & Angela R. Wu & Norma F. Neff & Gary L. Mantalas & F. Hernan Espinoza & Tushar J. Desai & Mark A. Krasnow & Stephen R. Quake, 2014. "Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq," Nature, Nature, vol. 509(7500), pages 371-375, May.
    4. 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.
    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.
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