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

Dev Cell. 2020 Apr 6;53(1):117-128.e6. doi: 10.1016/j.devcel.2020.01.033. Epub 2020 Feb 27.


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.

Keywords: basal cell; human development; lung; lung development; lung organoid; organoid; single-cell RNA-seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Epithelial Cells / cytology*
  • Humans
  • Lung / cytology
  • Organoids / cytology*
  • Pluripotent Stem Cells / cytology*
  • Tissue Engineering / methods