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Interlocking core regulatory circuits enable viral hijacking in Merkel cell carcinoma

ABSTRACT: Interlocking core regulatory circuits enable viral hijacking in Merkel cell carcinoma

PROVIDER: PRJNA1088415 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28353040.fastq.gz	Fastqsanger.gz
	SRR28353041.fastq.gz	Fastqsanger.gz
	SRR28353042.fastq.gz	Fastqsanger.gz
	SRR28353043.fastq.gz	Fastqsanger.gz
	SRR28353044.fastq.gz	Fastqsanger.gz

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Interlocking core regulatory circuits enable viral hijacking in Merkel cell carcinoma

Project description:Merkel Cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The conditions and cell type(s) of MCC are unknown. Virus positive MCC (VP-MCC) is driven by T antigens expressed from integrated Merkel cell polyomavirus (MCPyV). We found that VP-MCC required lineage-specific neuroendocrine transcription factors (TFs), including ATOH1, INSM1, ISL1, LHX3, POU4F3, and SOX2 that were central to core regulatory (CR) transcriptional circuitry. MCPyV small T antigen and host CR TFs co-bound VP-MCC super enhancers while T antigen expression was directly regulated by LHX3 and ISL1, establishing an interlocking network between host CR circuitry and the oncovirus. Moreover, MCPyV integration sites were enriched near VP- MCC super enhancers, further suggesting a functional relationship between viral oncogenesis and core neuroendocrine circuitry.

2025-05-24 | GSE261681 | GEO

Comparative Transcriptional Profiling of human Merkel cells and Merkel Cell Carcinoma

Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCV+ Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and down-regulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. Two-conditions experiment, MCV vs Normal Merkel Cell. Biological replicates : 4 MCV (Cy5), 1 control = pool of Normal Merkel cells from 3 liftings

2014-01-01 | E-GEOD-50434 | biostudies-arrayexpress

Comparative Transcriptional Profiling of Human Merkel cells and Merkel Cell Carcinoma

Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCPyV(+) Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and downregulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy.

2014-01-01 | GSE50434 | GEO

Characterization of human Merkel cells and their response to Merkel cell polyomavirus

Project description:Merkel cells are epidermal mechanoreceptor cells responsible for the perception of gentle touch. Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer. Although MCC histologically resembles Merkel cells, the cell of origin for MCC is unknown. MCC frequently contains integrated Merkel cell polyomavirus (MCPyV), a small DNA tumor virus with widespread prevalence. Whether MCPyV can transform Merkel cells is unknown. Here, we describe the isolation and long-term expansion of human Merkel cells from neonatal foreskin. We validated the expression of several Merkel cell-related factors by RNASeq, and assessed the ultrastructure by electron microscopy. Culture of Merkel cell preparations on an artificial basement membrane promoted the formation of structures containing both Merkel and non-Merkel cell populations. To determine whether Merkel cells were susceptible to transformation, we expressed tumor-derived MCPyV T antigens and additional oncogenes. We were unable to demonstrate tumorigenesis in immunodeficient mice, but were able to detect T antigen expression from excised cells weeks after implantation. These results highlight that foreskin-isolated Merkel cells can be propagated extensively, sustain expression of MCPyV T antigens, but are not susceptible to transformation by MCPyV, suggesting that Merkel cells from non-glabrous skin may not be a cell of origin for MCC.

2017-04-01 | GSE79657 | GEO

microRNA expression patterns related to merkel cell polyomavirus infection and clinical outcomes in human merkel cell carcinoma

Project description:We performed miRNA expression profiling in a series of human Merkel Cell carcinoma samples using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 723 human miRNAs was used to determine miRNA expression profiles in 16 human Merkel cell carcinoma (MCC) samples. To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.

2013-12-31 | E-GEOD-43699 | biostudies-arrayexpress

Merkel cell formation in hairy and glabrous skin

Project description:We describe Merkel cell formation in glabrous skin during embryogenesis. In our study, we first found that Merkel cells were specified at E15.5, 24 hours later, comparing to the back skin. Interestingly, by performing lineage-tracing experiments, we found that unlike back skin, SOX9(+) cells do not give rise to Merkel cells in glabrous skin. We performed transcriptional profiling of Merkel cells of the back and glabrous skin and showed that their transcriptoms are very similar. Taken together, Merkel cells in back skin and glabrous skin are similar, and their formation is controlled by a common genetic program, although their precursor cells might differ.

2021-11-14 | GSE122598 | GEO

Comparative genomic hybridization of human Merkel cell carcinoma tumors

Project description:Array-CGH profiles of Merkel cell carcinoma tumors Experiment Overall Design: We perfromed array-CGH on 25 Merkel cell carcinoma tumor samples (2 primary/metastasis pairs) looking for recurrent gains/losses among the cohort of tumors. Experiment Overall Design: Results from the Analysis of Copy Errors (ACE) may be found in GSE13239_MccACEAnalyzedData.txt. Experiment Overall Design: The overall profiles of the primary/metastasis pairs are similar. These metastases samples, 1m and 3m, were excluded from the ACE analysis.

2009-01-14 | E-GEOD-13239 | biostudies-arrayexpress

Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

Project description:Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to directly test this hypothesis. RNA sequencing of adult Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of b2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch.

2018-11-08 | GSE114336 | GEO

Array Comparative Genomic Hybridization of Merkel Cell Carcinoma Tumors

Project description:Array-CGH profiles of Merkel cell carcinoma tumors Keywords: fresh frozen and formalin fixed paraffin embedded primary tumor, nodal and metastasis merkel cell carcinoma tumor samples

2009-01-01 | GSE13239 | GEO

Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells

Project description:Super-enhancer-associated core regulatory circuits mediate susceptibility to retinoic acid in neuroblastoma cells

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