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Conversion of Sox2-Dependent Merkel Cell Carcinoma to a Differentiated Neuron-like Phenotype by T Antigen Inhibition

ABSTRACT: Conversion of Sox2-Dependent Merkel Cell Carcinoma to a Differentiated Neuron-like Phenotype by T Antigen Inhibition

PROVIDER: PRJNA563893 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10067572.fastq.gz	Fastqsanger.gz
	SRR10067573.fastq.gz	Fastqsanger.gz
	SRR10067574.fastq.gz	Fastqsanger.gz
	SRR10067575.fastq.gz	Fastqsanger.gz
	SRR10067576.fastq.gz	Fastqsanger.gz

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Conversion of Sox2-Dependent Merkel Cell Carcinoma to a Differentiated Neuron-like Phenotype by T Antigen Inhibition

Project description:Keratinocyte-cocultured Merkel cell carcinoma cell line (MCC) CVG-1 cells transduced with contorl shRNA (shCtrl) and viral T antigen targeting shRNA (shpanT) were sequenced using the 10x Genomics platform in order to analyze transcriptional changes associated with MCC cancer cell differentiation into neuron-like cells on a single cell level.

2019-09-05 | GSE136867 | GEO

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.

Project description:Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV+ MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including HES6, SOX2, ATOH1, and KRT20 Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV+ MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor.

| S-EPMC6778204 | biostudies-literature

Mitochondrial reprogramming using dCas9 boosts glia-to-neuron conversion

Project description:Astrocyte-to-neuron conversion has developed into a promising avenue for neuronal replacement therapy. Neurons depend critically on mitochondria function and often die by ferroptosis during the conversion process. Here we examined the extent of adequate mitochondrial reprogramming by morphology and proteome analysis. While mitochondria profoundly changed their morphology during Neurogenin2 (Neurog2) – or Achaete-scute homolog 1 (Ascl1)-mediated astrocyte-to-neuron reprogramming, we found neuron-specific mitochondrial proteins, here identified in a comprehensive proteome analysis of isolated mitochondria from primary neurons and astrocytes, to be only partially and at late stages regulated during the process. To improve this, we used dCas9 technology to induce neuron-specific mitochondrial proteins early during reprogramming. This resulted not only in increased conversion efficiency, but also in faster neuronal generation. Taken together, reprogramming mitochondria in a cell type-specific manner has powerful effects on astrocyte-to-neuron conversion, suggesting mitochondria to be a driving force in this process.

2021-03-29 | PXD014886 | Pride

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

Timeline RNAseq of fibroblast to neuron direction conversion

Project description:Timeline RNAseq of fibroblast to neuron direction conversion

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RNA-seq timeline of fibroblast to neuron conversion using traditional NC media and NC+ZPAK media

Project description:Bulk RNA was extracted via trizol at Fibroblasts stage, 5 days, 10 days, 15 days, and 20 days of fibroblast to neuron conversion using traditional NC media, or NC media supplemented with ZM336372, pyrintegrin, AZ960, and KC7F2

2019-05-23 | E-MTAB-7250 | 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

RNA-seq analysis of gene expression in cells during Ascl1 mediated astrocyte-to-neuron conversion.

Project description:We analyzed the transcriptomic changes in cells sorted from astrocyte-to-neuron conversion at different stages, identified the differentially expressed genes (DEGs), and functionally validated the critical DEGs.

2020-12-29 | GSE132674 | GEO

Identification the Expression of Sox2 in Colorectal Cancer Tissues

Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.

| 2124687 | ecrin-mdr-crc

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