Whereas SARS-CoV-2 utilizes cathepsins to enter most cell lines, human airway organoids revealed that entry into relevant cells is dependent on serine proteases, which can be targeted for treatment.
Building on previous work (Dye et al., 2015) showing that pluripotent stem cell derived lung organoids were immature/fetal, the current study shows that in vivo transplantation leads to mature tissue, reminiscent of adult airways.
Cell culture adaptation of SARS-CoV-2 is prevented on human airway cells with an active serine protease-mediated entry pathway, allowing the production of genetically stable virus stocks for laboratory experiments.
An integrated stem cell-based disease modeling and computational approach demonstrates how proximal airway epithelium is critical for SARS-CoV-2 infectivity and distal alveolar cells are critical for simulating the host responses.
The balance between SOX2 and SOX21 is evolutionary conserved and is important for cell fate decision during lung epithelium development and repair after damage.
Directed differentiation of stem cells can generate ventral-anterior foregut spheroids that can expand into three-dimensional lung organoids with striking structural, cellular and molecular similarities to the human fetal lung.
A combination of unbiased scRNA-sequencing and functional approaches in organoid cultures and injury-repair models in vivo reveals major heterogeneity in adult murine airway basal cells, which is established prenatally and conserved in humans.
Improved characterisation of human embryonic lung development highlights human-mouse differences and facilitates the development of defined culture conditions for the expansion of self-renewing, multipotent human lung epithelial progenitor cells.
Konstantinos Gkatzis, Paolo Panza ... Didier YR Stainier
A serum-free organotypic culture model of mouse lung epithelial progenitors was developed and used to screen WNT modulators for regulators of epithelial differentiation.
To facilitate human developmental biology research, CRISPR-mediated homologous recombination, tightly inducible gene knockdowns (CRISPRi) and overexpression (CRISPRa) have been efficiently applied to human organoids.
