Nov 4, 2018

Basal stem cell fate specification is mediated by SMAD signaling in the developing human lung

BioRxiv : the Preprint Server for Biology
Alyssa J MillerJason R Spence

Abstract

Basal stem cells (basal cells), located in the bronchi and trachea of the human lung epithelium, play a critical role in normal airway homeostasis and repair, and have been implicated in the development of diseases such as cancer. Additionally, basal-like cells contribute to alveolar regeneration and fibrosis following severe injury. However, the developmental origin of basal cells in humans is unclear. Previous work has shown that specialized progenitor cells exist at the tips of epithelial tubes during lung branching morphogenesis, and in mice, give rise to all alveolar and airway lineages. These bud tip progenitor cells have also been described in the developing human lung, but the mechanisms controlling bud tip differentiation into specific cell lineages, including basal cells, are unknown. Here, we interrogated the bud tip-to-basal cell transition using human tissue specimens, bud tip progenitor organoid cultures, and single-cell transcriptomics. We used single-cell mRNA sequencing (scRNAseq) of developing human lung specimens from 15-21 weeks gestation to identify molecular signatures and cell states in the developing human airway epithelium. We then inferred differentiation trajectories during bud tip-to-airway different...Continue Reading

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Mentioned in this Paper

Biological Markers
Cell Fate
Regenerative Medicine
Catheter Tip
Lung
Bone morphogenetic protein 4
Smad1
Alveolar
Trachea
Tgfb1

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