Acquisition of alveolar fate and differentiation competence by human fetal lung epithelial progenitor cells
Lim, K.; Tang, W.; Sun, D.; He, P.; Teichmann, S.; Marioni, J. C.; Meyer, K. B.; Rawlins, E. L.
10.1101/2021.06.30.450501 bioRxivShow abstract
Variation in lung alveolar development is strongly linked to disease susceptibility. However, the cellular and molecular mechanisms underlying alveolar development are difficult to study in humans. Using primary human fetal lungs we have characterized a tip progenitor cell population with alveolar fate potential. These data allowed us to benchmark a self-organising organoid system which captures key aspects of lung lineage commitment and can be efficiently differentiated to alveolar type 2 cell fate. Our data show that Wnt and FGF signalling, and the downstream transcription factors NKX2.1 and TFAP2C, promote human alveolar or airway fate respectively. Moreover, we have functionally validated cell-cell interactions in human lung alveolar patterning. We show that Wnt signalling from differentiating fibroblasts promotes alveolar type 2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. Our organoid system recapitulates key aspects of human lung development allowing mechanistic experiments to determine the underpinning molecular regulation.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Niche-driven phenotypic plasticity and cis-regulatory dynamics of a revised model for intestinal secretory differentiation 96%
- Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation 96%
- Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis 96%
Similar papers in this journal
- Release of Notch activity coordinated by IL-1β signalling confers differentiation plasticity of airway progenitors via Fosl2 during alveolar regeneration 99%
- A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium 97%
- Combinatorial selective ER-phagy remodels the ER during neurogenesis 97%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.