ATACseq comparison of mouse tracheal pseudostratified vs hillock basal stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1063667 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27503790_1.fastq.gz | Fastqsanger.gz | |||
| SRR27503790_2.fastq.gz | Fastqsanger.gz | |||
| SRR27503791_1.fastq.gz | Fastqsanger.gz | |||
| SRR27503791_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
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.
2024-03-05 | GSE253020 | GEO
Project description:Mouse tracheal pseudostratified vs hillock basal stem cells
| PRJNA1063662 | ENA
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.
2024-03-05 | GSE253021 | GEO
Project description:RNAseq transcriptomic comparison of mouse tracheal pseudostratified vs hillock basal stem cells
| PRJNA1063665 | ENA
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.
2025-01-27 | GSE266853 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-05 | GSE253023 | GEO
Project description:Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broader landscape of intra-tumoral heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13+ hillock-like population of slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The tumor hillock-like state is conserved across multiple animal models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumors. Our findings shed light on the cellular origins of lung hillock-like states: normal club cells give rise to tumors with luminal hillock-like populations, while basal-like tumor-propagating cells transition into basal hillock-like states, resembling homeostatic cellular responses to lung injury. Mechanistically, we identify KLF4 as a key transcriptional regulator of the hillock-like state, both necessary and sufficient to induce KRT13 expression. Together, these results provide new molecular insights into cell fate plasticity that underlies intra-tumoral heterogeneity in LUSC, offering potential avenues for new therapeutic strategies.
2026-05-27 | GSE316413 | GEO
Project description:Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broader landscape of intra-tumoral heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13+ hillock-like population of slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The tumor hillock-like state is conserved across multiple animal models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumors. Our findings shed light on the cellular origins of lung hillock-like states: normal club cells give rise to tumors with luminal hillock-like populations, while basal-like tumor-propagating cells transition into basal hillock-like states, resembling homeostatic cellular responses to lung injury. Mechanistically, we identify KLF4 as a key transcriptional regulator of the hillock-like state, both necessary and sufficient to induce KRT13 expression. Together, these results provide new molecular insights into cell fate plasticity that underlies intra-tumoral heterogeneity in LUSC, offering potential avenues for new therapeutic strategies.
2026-05-27 | GSE316412 | GEO
Project description:Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broader landscape of intra-tumoral heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13+ hillock-like population of slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The tumor hillock-like state is conserved across multiple animal models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumors. Our findings shed light on the cellular origins of lung hillock-like states: normal club cells give rise to tumors with luminal hillock-like populations, while basal-like tumor-propagating cells transition into basal hillock-like states, resembling homeostatic cellular responses to lung injury. Mechanistically, we identify KLF4 as a key transcriptional regulator of the hillock-like state, both necessary and sufficient to induce KRT13 expression. Together, these results provide new molecular insights into cell fate plasticity that underlies intra-tumoral heterogeneity in LUSC, offering potential avenues for new therapeutic strategies.
2026-05-27 | GSE290746 | GEO
Project description:Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broader landscape of intra-tumoral heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13+ hillock-like population of slower-dividing tumor cells characterized by immunomodulatory gene expression signatures. The tumor hillock-like state is conserved across multiple animal models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumors. Our findings shed light on the cellular origins of lung hillock-like states: normal club cells give rise to tumors with luminal hillock-like populations, while basal-like tumor-propagating cells transition into basal hillock-like states, resembling homeostatic cellular responses to lung injury. Mechanistically, we identify KLF4 as a key transcriptional regulator of the hillock-like state, both necessary and sufficient to induce KRT13 expression. Together, these results provide new molecular insights into cell fate plasticity that underlies intra-tumoral heterogeneity in LUSC, offering potential avenues for new therapeutic strategies.
2026-05-27 | GSE290745 | GEO