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ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

ABSTRACT: ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

PROVIDER: PRJNA631967 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11777716_1.fastq.gz	Fastqsanger.gz
	SRR11777716_2.fastq.gz	Fastqsanger.gz
	SRR11777717_1.fastq.gz	Fastqsanger.gz
	SRR11777717_2.fastq.gz	Fastqsanger.gz
	SRR11777718_1.fastq.gz	Fastqsanger.gz

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ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

Project description:The role of POU4F3 in Merkel cell maturation, but not induction, is similar to its role in hair cells. This prompted us to investigate whether POU4F3 also regulates the accessibility of ATOH1 targets in a feed-forward manner during the maturation of Merkel cells. Our results suggest that, just as in hair cells, the pioneer factor activity of POU4F3 is also required for ATOH1 to correctly coordinate mechanosensory differentiation in Merkel cells.

2021-07-09 | GSE150388 | GEO

ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

Project description:ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

| PRJNA631967 | ENA

Identification of the epithelial progenitor niche for the Merkel cell lineage

Project description:Transcriptional profile of murine touch dome keratinocytes sorted on the basis of alpha6-integrin, CD34, Sca1 and CD200 surface markers. Compared to the transcriptional profile of murine interfollicular epidermis (IFE) without the touch dome keratinocytes

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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.

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ATACseq, CutnRun and RNAseq data from sensory progenitors and hair cells, from wild type and Pou4f3-mutant cochlea

Project description:Hearing and balance are mediated in vertebrates by inner ear mechanosensory hair cells. Hair cell development, maturation and survival require POU4F3, a class IV POU domain transcription factor that is expressed in hair cells shortly after they start to differentiate. Here, we show that POU4F3 has pioneer factor activity, and is necessary to promote chromatin accessibility at approximately half of the distal regulatory elements that appear as hair cells differentiate. Pou4f3 expression in the inner ear is initiated by ATOH1, a bHLH transcription factor that is also necessary for hair cell differentiation and survival. We show that ATOH1 also binds a large number of POU4F3-dependent distal regulatory elements, suggesting a synergistic feed-forward model in which ATOH1 induces POU4F3, which then acts to promote ATOH1-dependent hair cell differentiation.

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Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages.

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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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