Plasma amino acids regulate pancreatic acinar cell proliferation and size via mTORC1 and YAP/TAZ signaling pathways
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019633 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26133237_1.fastq.gz | Fastqsanger.gz | |||
| SRR26133237_2.fastq.gz | Fastqsanger.gz | |||
| SRR26133238_1.fastq.gz | Fastqsanger.gz | |||
| SRR26133238_2.fastq.gz | Fastqsanger.gz | |||
| SRR26133239_1.fastq.gz | Fastqsanger.gz |
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Project description:Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells to lose cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lungs. Significantly, this cell fate conversion is mediated via distinctive transitional cell states of Damage-Associated Transient Progenitors (DATPs), recently known to emerge during injury repair, in mouse and human lungs. Further, YAP/TAZ signaling is identified to realign the amino acid metabolism by modulating mTORC1-ATF4 activity, which is integral to fate conversion of secretory cells into AT1 fate. We observed aberrant activation of the YAP/TAZ-mTORC1-ATF4 axis in the altered airway epithelium of human pulmonary fibrosis where the emergence of DATPs and A1 cells is prominent. Finally, genetic and pharmacologic inhibition of mTORC1 activity restores lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases.
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Project description:Activation of YAP/TAZ signaling reprograms the airway secretory cell fate via mTORC1-dependent amino acid metabolism
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