RNAseq transcriptomic comparison of mouse tracheal pseudostratified vs hillock basal stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1063665 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27504430_1.fastq.gz | Fastqsanger.gz | |||
| SRR27504430_2.fastq.gz | Fastqsanger.gz | |||
| SRR27504431_1.fastq.gz | Fastqsanger.gz | |||
| SRR27504431_2.fastq.gz | Fastqsanger.gz | |||
| SRR27504432_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
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Project description:Mouse tracheal pseudostratified vs hillock basal stem cells
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Project description:Airway hillocks are stratified epithelial structures of unknown function. We show that the luminal cells of hillocks are squamous barrier cells that shield a unique population of underlying hillock basal stem cells. Hillocks occur in characteristic locations and persist for months in uninjured mice. Following injury, hillock basal stem cells undergo massive clonal expansion, resurface denuded airway, and demonstrate extreme plasticity, generating classic airway epithelium with its six component cell types. Remarkably, hillocks resist a very broad spectrum of injuries, including toxins, infection, acid, and physical injury. Furthermore, hillock basal stem cells are characterized by enhanced expression associated with barrier function, cell adhesion, and retinoic acid catabolism. Indeed, hillock basal cells preferentially expand, stratify, and keratinize in the setting of retinoic acid signaling inhibition, a known clinical cause of squamous metaplasia. Finally, we identify human hillocks whose basal cells demonstrate preferential sensitivity to retinoic acid inhibition and conserved barrier properties. Given their capacity for clonal expansion, their plasticity, and their retinoic acid sensitivity, the existence of hillocks and hillock basal stem cells have broad implications for injury repair and for defining the origin of squamous metaplasia, long thought to be a precursor of lung cancer.
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Project description:ATACseq comparison of mouse tracheal pseudostratified vs hillock basal stem cells
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Project description:Airway hillocks are stratified epithelial structures of unknown function. We show that the luminal cells of hillocks are squamous barrier cells that shield a unique population of underlying hillock basal stem cells. Hillocks occur in characteristic locations and persist for months in uninjured mice. Following injury, hillock basal stem cells undergo massive clonal expansion, resurface denuded airway, and demonstrate extreme plasticity, generating classic airway epithelium with its six component cell types. Remarkably, hillocks resist a very broad spectrum of injuries, including toxins, infection, acid, and physical injury. Furthermore, hillock basal stem cells are characterized by enhanced expression associated with barrier function, cell adhesion, and retinoic acid catabolism. Indeed, hillock basal cells preferentially expand, stratify, and keratinize in the setting of retinoic acid signaling inhibition, a known clinical cause of squamous metaplasia. Finally, we identify human hillocks whose basal cells demonstrate preferential sensitivity to retinoic acid inhibition and conserved barrier properties. Given their capacity for clonal expansion, their plasticity, and their retinoic acid sensitivity, the existence of hillocks and hillock basal stem cells have broad implications for injury repair and for defining the origin of squamous metaplasia, long thought to be a precursor of lung cancer.
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Project description:Inhibiting the androgen receptor (AR) is effective for advanced prostate cancers because of their AR-dependent luminal epithelial cell identity. Tumors progress during therapy to castration resistant prostate cancer (CRPC) by restoring AR signaling and maintaining luminal identity or by converting through lineage plasticity to a neuroendocrine identity (NEPC) or double negative CRPC lacking luminal and neuroendocrine identity (DNPC). Here, we show that DNPC cells express genes defining basal, club, and hillock epithelial cells from benign prostate. We identified KLF5 as a regulator of DNPC growth and expression of genes defining this mixed basal, club, and hillock cell identity. KLF5-mediated upregulation of RARG exposed a DNPC growth sensitivity to retinoic acid receptor agonists, which down-regulated KLF5 and up-regulated AR. These findings offer new CRPC classifications based on prostate epithelial cell identities, and nominate KLF5 and RARG as therapeutic targets for CRPC displaying a mixed basal, club, and hillock identity.
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