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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.

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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

2010-11-15 | E-MEXP-2925 | 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.

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

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

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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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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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Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [RNA-seq]

Project description:Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [RNA-seq]

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Project description:Tenascin-C expressing touch dome keratinocytes exhibit characteristics of all epidermal lineages [ATAC-seq]

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Project description:Merkel cells (MCs), specialized neuroendocrine touch sensors within the epidermis, play a crucial role in tactile sensation. To gain deeper insignts into their molecular characteristics, we employed RNA sequencing (RNA-seq) to explore the transcriptome of MCs in comparsion to basal keratinocytes in neonatal mouse skin.

2024-06-01 | GSE264433 | GEO

POU4F3 Pioneer Activity Enables ATOH1 to Drive Diverse Mechanoreceptor Differentiation Through a Feed-Forward Epigenetic Mechanism

Project description:During embryonic development, hierarchical cascades of transcription factors interact with lineage specific chromatin structures to control the sequential steps in the differentiation of specialized cell types. While examples of transcription factor cascades have been well documented, the mechanisms underlying developmental changes in accessibility of cell type-specific enhancers remain poorly understood. Here we show that the transcriptional ‘master regulator’, ATOH1 – which is necessary for the differentiation of two distinct mechanoreceptor cell types, hair cells in the inner ear, and Merkel cells of the epidermis – is unable to access much of its target enhancer network in the progenitor populations of either cell type when it first appears, imposing a block to further differentiation. This block is overcome by a feed-forward mechanism in which ATOH1 first stimulates expression of POU4F3, which subsequently acts as a pioneer factor to provide access to closed ATOH1 enhancers, allowing hair cell and Merkel cell differentiation to proceed. Our analysis also indicates the presence of both shared and divergent ATOH1/POU4F3-dependent, enhancer networks in hair cells and Merkel cells. These cells share a deep developmental lineage relationship, deriving from their common epidermal origin, and suggesting that this feed-forward mechanism preceded the evolutionary divergence of these very different mechanoreceptive cell types.

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