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Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme

Author

Listed:
  • Andrea B. Alber

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • Hector A. Marquez

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • Liang Ma

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • George Kwong

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • Bibek R. Thapa

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • Carlos Villacorta-Martin

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Jonathan Lindstrom-Vautrin

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Pushpinder Bawa

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Feiya Wang

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Yongfeng Luo

    (Keck School of Medicine, University of Southern California)

  • Laertis Ikonomou

    (University at Buffalo
    Jacobs School of Medicine and Biomedical Sciences, University at Buffalo)

  • Wei Shi

    (University of Cincinnati College of Medicine)

  • Darrell N. Kotton

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

Abstract

While the generation of many lineages from pluripotent stem cells has resulted in basic discoveries and clinical trials, the derivation of tissue-specific mesenchyme via directed differentiation has markedly lagged. The derivation of lung-specific mesenchyme is particularly important since this tissue plays crucial roles in lung development and disease. Here we generate a mouse induced pluripotent stem cell (iPSC) line carrying a lung-specific mesenchymal reporter/lineage tracer. We identify the pathways (RA and Shh) necessary to specify lung mesenchyme and find that mouse iPSC-derived lung mesenchyme (iLM) expresses key molecular and functional features of primary developing lung mesenchyme. iLM recombined with engineered lung epithelial progenitors self-organizes into 3D organoids with juxtaposed layers of epithelium and mesenchyme. Co-culture increases yield of lung epithelial progenitors and impacts epithelial and mesenchymal differentiation programs, suggesting functional crosstalk. Our iPSC-derived population thus provides an inexhaustible source of cells for studying lung development, modeling diseases, and developing therapeutics.

Suggested Citation

  • Andrea B. Alber & Hector A. Marquez & Liang Ma & George Kwong & Bibek R. Thapa & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Pushpinder Bawa & Feiya Wang & Yongfeng Luo & Laertis Ikonomou , 2023. "Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39099-9
    DOI: 10.1038/s41467-023-39099-9
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    References listed on IDEAS

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    1. Lu Han & Praneet Chaturvedi & Keishi Kishimoto & Hiroyuki Koike & Talia Nasr & Kentaro Iwasawa & Kirsten Giesbrecht & Phillip C. Witcher & Alexandra Eicher & Lauren Haines & Yarim Lee & John M. Shanno, 2020. "Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Keishi Kishimoto & Kana T. Furukawa & Agustin Luz-Madrigal & Akira Yamaoka & Chisa Matsuoka & Masanobu Habu & Cantas Alev & Aaron M. Zorn & Mitsuru Morimoto, 2020. "Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Laertis Ikonomou & Michael J. Herriges & Sara L. Lewandowski & Robert Marsland & Carlos Villacorta-Martin & Ignacio S. Caballero & David B. Frank & Reeti M. Sanghrajka & Keri Dame & Maciej M. Kańduła , 2020. "The in vivo genetic program of murine primordial lung epithelial progenitors," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
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