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Host response to Merkel cell polyomavirus oncogenes in neonatal human dermal fibroblast

ABSTRACT: Host response to Merkel cell polyomavirus oncogenes in neonatal human dermal fibroblast

PROVIDER: PRJNA1166677 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30830000_1.fastq.gz	Fastqsanger.gz
	SRR30830000_2.fastq.gz	Fastqsanger.gz
	SRR30830001_1.fastq.gz	Fastqsanger.gz
	SRR30830001_2.fastq.gz	Fastqsanger.gz
	SRR30830002_1.fastq.gz	Fastqsanger.gz

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Host response to Merkel cell polyomavirus oncogenes in neonatal human dermal fibroblast

Project description:Merkel cell polyomavirus (MCPyV) early region (ER) and vector control inducible vectors were introduced into neonatal human dermal fibroblasts (nHDFs). Total RNA was then extracted and sequenced in triplicate at 0, 48 and 96 hours post-induction with doxycycline treatment. The purpose of this experiment was to identify the host response to MCPyV ER at the transcriptomic level, using both differential expression analysis and transcriptional network reconstruction. Together with our previous IMR90 model, we aim to systematically understand the initial steps toward Merkel cell carcinoma in different potential precursor cell types.

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Project description:Dynamics of host response to Merkel cell polyomavirus oncogenes

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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.

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