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In Vitro and In Vivo Development of the Human Airway at Single-Cell Resolution.
Journal article

In Vitro and In Vivo Development of the Human Airway at Single-Cell Resolution.

  • Miller AJ Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Yu Q Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; University of Basel, Basel, Switzerland; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
  • Czerwinski M Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Tsai YH Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Conway RF Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Wu A Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Holloway EM Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Walker T Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Glass IA Department of Pediatrics, Genetic Medicine, University of Washington, Seattle, WA 98195, USA.
  • Treutlein B Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. Electronic address: barbara.treutlein@bsse.ethz.ch.
  • Camp JG Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; University of Basel, Basel, Switzerland; Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. Electronic address: grayson.camp@iob.ch.
  • Spence JR Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI 48109, USA. Electronic address: spencejr@umich.edu.
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  • 2020-02-29
Published in:
  • Developmental cell. - 2020
basal cell
human development
lung
lung development
lung organoid
organoid
single-cell RNA-seq
Cell Differentiation
Epithelial Cells
Humans
Lung
Organoids
Pluripotent Stem Cells
Tissue Engineering
English Bud tip progenitor cells give rise to all murine lung epithelial lineages and have been described in the developing human lung; however, the mechanisms controlling human bud tip differentiation into specific lineages are unclear. Here, we used homogeneous human bud tip organoid cultures and identified SMAD signaling as a key regulator of the bud tip-to-airway transition. SMAD induction led to the differentiation of airway-like organoids possessing functional basal cells capable of clonal expansion and multilineage differentiation. To benchmark in vitro-derived organoids, we developed a single-cell mRNA sequencing atlas of the human lung from 11.5 to 21 weeks of development, which revealed high degrees of similarity between the in vitro-derived and in vivo airway. Together, this work sheds light on human airway differentiation in vitro and provides a single-cell atlas of the developing human lung.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/188505
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