Single cell mRNA sequencing on esophageal cells after HH pathway activation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA626005 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11564221.fastq.gz | Fastqsanger.gz | |||
| SRR11564222.fastq.gz | Fastqsanger.gz | |||
| SRR11564223.fastq.gz | Fastqsanger.gz | |||
| SRR11564224.fastq.gz | Fastqsanger.gz | |||
| SRR11564225.fastq.gz | Fastqsanger.gz |
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Project description:In this study we used single cell mRNA sequencing to explore heterogeneity of the fate induced by hedgehog (HH) pathway activation in esophageal cells. We merged the data from the two samples and filtered the merged data to work only with cells expressing the SmoM2-YFP protein (2,413 cells). Using UMAP reduction, we observed 10 clusters with a resolution set at 0.3. Among these clusters, we identified clusters of squamous esophagus epithelial cells but also one cluster enriched for many columnar markers. These results show that activation of the HH pathway in esophageal keratinocytes leads to multiple cell phenotypes including a columnar epithelial one in a minority of keratinocytes.
2021-04-20 | GSE148875 | GEO
Project description:RNA-seq and ATAC-sequencing of esophageal cells after HH pathway activation
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Project description:Purpose: Most Hedgehog responsive gene expression is mediated through GLI de-repression. Additionally GLI -repression is proposed to play roles in limb pre-patterning before HH pathway activation. This study evaluates if GLI repression is established prior to HH pathway activation. Methods: To determine if GLI-repression is established prior to pathway activation, we used genomic approaches to study GLI-mediated repression using the mouse developing limb as a model. We identified pre-HH (E9.25, 21-23S) and post-HH (E10.5, 32-25S) GLI3 binding regions using CUT&RUN for endogenous FLAG-tagged GLI3 proteins. Using a combination of ChIP-seq, CUT&RUN, CUT&Tag, ATAC-seq and RNA-seq, we tested whether loss of Gli3 prior to HH signaling was able to de-repress genes and enhancers, as it does after HH signaling. Results: Prior to HH signaling, GLI3 binds to poised, accessible regions with histone deacetylase (HDAC) proteins, similar to post-HH signaling. Despite GLI3 binding to most regions as it does in the post-HH limb, loss of Gli3 is unable to prematurely active target genes or enhancers. Furthermore, we find that GLI3-dependent chromatin compaction does not occur until roughly 10 hours after HH signaling would have normally been induced. Collectively, these results support that GLI repressor proteins are inert prior to HH pathway activation.
2022-01-21 | GSE178838 | GEO
Project description:GLI transcriptional repression is inert prior to HH pathway activation
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Project description:In this study, we used RNA sequencing to characterize esophageal progenitors following activation of the hedgehog (HH) pathway in vivo. We observed two main fates following activation of the HH pathway in the squamous epithelium: one population is in an intermediate state between squamous and columnar epithelium, and another achieves a full columnar conversion. We compared these 2 populations to different FACS sorted epithelial cells from different tissues of the gastro-intestinal tract (adult esophagus, embryonic esophagus, transition epithelium from the stomach, corpus of the stomach and small intestine). Our results suggest a multistep process in which esophageal progenitors first turn on a transcriptomic program that resembles the one from embryonic esophagus, then, a subset of these dedifferentiated cells can turn on a columnar differentiation program that shares similarities with intestinal cells. Collectively, these data demonstrate that some esophageal cells can be reprogrammed to generate columnar cells in vivo.
2021-04-20 | GSE148874 | GEO
Project description:The Hedgehog (Hh) signaling pathway is essential for embryonic development and tissue homeostasis, and its dysregulation contributes to severe developmental disorders and various cancers. Despite its biological importance, a detailed understanding of the dynamic interactions and phosphorylation events that regulate this pathway remains incomplete. To address this gap, we employed a comprehensive systems-level approach combining proximity-dependent biotinylation (BioID), phosphoproteomics, and advanced computational analyses to generate an extensive and dynamic map of the mammalian Hh signaling pathway. Using stable NIH-3T3 and HEK293 cell lines expressing key Hh components, we systematically characterized protein-protein interactions (PPIs) and phosphorylation dynamics in response to pathway activation and during primary cilia progression. Our workflow identified numerous ciliary proteins, highlighting the essential role of primary cilia and phosphorylation in Hh signaling regulation. To further explore the contribution of primary cilia, we analyzed interaction networks during cilia absence, formation, and resorption. These analyses revealed that the mammalian Hh signaling network is modular, consisting of four distinct functional groups: core membrane/ciliary regulators, intracellular signaling regulators, trafficking/scaffolding regulators, and downstream transcriptional regulators. Each module displayed specialized roles within the signaling cascade, closely linked to cell cycle regulation.
2025-03-17 | MSV000097352 | MassIVE
Project description:In this study, we used ATAC sequencing to compare the chromatin landscape of esophageal cells in which hedgehog (HH) pathway has been activated (K5SmoM2), to control esophageal cells (WT). We identified more than 50% of the peaks differentially opened in both conditions. Among these differentially opened peaks in EpHI cells, we identified chromatin regions in key columnar markers. Taken together these results show that HH pathway activation triggers chromatin landscape remodeling to facilitate transcommitment.
2021-04-20 | GSE148872 | GEO
Project description:Attenuation of Hedgehog (Hh) pathway activity leads to accelerated tumor progression in a mouse model of N-butyl-N-4-hydroxybutyl nitrosamine (BBN) – induced bladder carcinoma. In order to identify genes regulated by the Hh pathway that might be involved in bladder cancer progression, we performed transcriptional profiling of bladders harvested from mice after BBN-exposure, comparing Gli1CreER/WT; Smoflox/WT mice to Gli1CreER/WT; Smoflox/flox mice, which express CreER under control of the Gli1 promoter and carry one or two floxed alleles of the essential Hh pathway transductory component Smoothened (Smo) respectively. Administration of Tamoxifen to these mice results in attenuation of Hh pathway activty to a greater extent in the Gli1CreER/WT;Smoflox/flox mice as compared to Gli1CreER/WT;Smoflox/WT mice, allowing identification of Hh-pathway regulated genes. 6 total samples were analyzed. 3 bladders from Gli1CreER/WT; Smoflox/WT mice and 3 bladders from Gli1CreER/WT; Smoflox/flox mice were analyzed.
2014-08-27 | E-GEOD-60654 | biostudies-arrayexpress
Project description:Attenuation of Hedgehog (Hh) pathway activity leads to accelerated tumor progression in a mouse model of N-butyl-N-4-hydroxybutyl nitrosamine (BBN) – induced bladder carcinoma. In order to identify genes regulated by the Hh pathway that might be involved in bladder cancer progression, we performed transcriptional profiling of bladders harvested from mice after BBN-exposure, comparing Gli1CreER/WT; Smoflox/WT mice to Gli1CreER/WT; Smoflox/flox mice, which express CreER under control of the Gli1 promoter and carry one or two floxed alleles of the essential Hh pathway transductory component Smoothened (Smo) respectively. Administration of Tamoxifen to these mice results in attenuation of Hh pathway activty to a greater extent in the Gli1CreER/WT;Smoflox/flox mice as compared to Gli1CreER/WT;Smoflox/WT mice, allowing identification of Hh-pathway regulated genes.
2014-08-27 | GSE60654 | GEO
Project description:Aberrant sonic hedeghog signaling is implicated in the development of various cancer entities such as medulloblastoma. The canonical signaling cascade has been studied for years. Activation of GLI transcription factors was revealed as the driving force upon pathway activation. Phosphorylation by Proteinkinase A, Casein Kinase 1 and Glycogen Synthase Kinase 3 β has been found to influence the degradation of the GLI transcription factors. However, the deeper role of phosphorylation in the signal transduction remains unclear. We, therefore, applied comprehensive HPLC-MS/MS based phosphoproteomics to reveal phosphorylation dynamics underlying the chemical activation and inhibition of sonic hedgehog signaling in human medulloblastoma cells. Human medulloblastoma cells were treated with SAG (Hh pathway induction) and Vismodegib (Hh pathway inhibition) for 5 and 15 minutes. Our phosphoproteomic profiling revealed a central role of phosphorylation in the regulation of ciliary assembly, trafficking and signal transduction after 5 minutes treatment. ERK/MAPK signaling besides protein kinase A signaling and mTOR signaling were differentially regulated. Activation of Polo-like kinase 1 and inhibtion of Caseinkinase 2A1 was characteristic for Vismodegib treatment while SAG treatment induced Aurora kinase A activity. Distinctive phosphorylation of central players of sonic Hh signaling such as Smoothened, SUFU, Gli2 and Gli3 was obtained after 15 minutes treatment.
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