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Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung

Author

Listed:
  • Rajan Jain

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Christina E. Barkauskas

    (Allergy, and Critical Care Medicine, Duke Medicine)

  • Norifumi Takeda

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
    Present address: Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.)

  • Emily J. Bowie

    (Duke Medicine)

  • Haig Aghajanian

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Qiaohong Wang

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Arun Padmanabhan

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
    Present address: Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.)

  • Lauren J. Manderfield

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Mudit Gupta

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Deqiang Li

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

  • Li Li

    (Allergy, and Critical Care Medicine, Duke Medicine)

  • Chinmay M. Trivedi

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania
    Present address: University of Massachusetts Medical School, 368 Plantation Street, Worcester, Massachusetts 01605, USA.)

  • Brigid L. M. Hogan

    (Duke Medicine)

  • Jonathan A. Epstein

    (Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania)

Abstract

The plasticity of differentiated cells in adult tissues undergoing repair is an area of intense research. Pulmonary alveolar type II cells produce surfactant and function as progenitors in the adult, demonstrating both self-renewal and differentiation into gas exchanging type I cells. In vivo, type I cells are thought to be terminally differentiated and their ability to give rise to alternate lineages has not been reported. Here we show that Hopx becomes restricted to type I cells during development. However, unexpectedly, lineage-labelled Hopx+ cells both proliferate and generate type II cells during adult alveolar regrowth following partial pneumonectomy. In clonal 3D culture, single Hopx+ type I cells generate organoids composed of type I and type II cells, a process modulated by TGFβ signalling. These findings demonstrate unanticipated plasticity of type I cells and a bidirectional lineage relationship between distinct differentiated alveolar epithelial cell types in vivo and in single-cell culture.

Suggested Citation

  • Rajan Jain & Christina E. Barkauskas & Norifumi Takeda & Emily J. Bowie & Haig Aghajanian & Qiaohong Wang & Arun Padmanabhan & Lauren J. Manderfield & Mudit Gupta & Deqiang Li & Li Li & Chinmay M. Tri, 2015. "Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7727
    DOI: 10.1038/ncomms7727
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    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. 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.

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