Ontology highlight
ABSTRACT:
PROVIDER: PRJNA561129 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9998943.fastq.gz | Fastqsanger.gz | |||
| SRR9998943_1.fastq.gz | Fastqsanger.gz | |||
| SRR9998943_2.fastq.gz | Fastqsanger.gz | |||
| SRR9998944.fastq.gz | Fastqsanger.gz | |||
| SRR9998944_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Keratins 5 and 14 are critical for cytoskeletal integrity, as shown by missense mutations in these genes, which cause the severe skin fragility disorder epidermolysis bullosa simplex (EBS). The complexity of the pathomechanisms in EBS is not fully understood and no effective management exists. In addition to fragility, EBS keratinocytes are characterized by aggregates of misfolded keratin. Here, we tested the chemical chaperone 4-phenylbutyrate (4-PBA) as a putative novel therapy, using keratinocytes from patients with severe generalized EBS due to distinct KRT5 and KRT14 mutations.
2019-12-03 | PXD010028 | Pride
Project description:The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity – nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed fragile nucleosomes throughout the yeast genome, nearly one thousand of which are at previously determined “nucleosome free” loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization. Comparing nucleosome occupancy under different MNase digestion levels and growth conditions.
2011-01-24 | E-GEOD-26412 | biostudies-arrayexpress
Project description:Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients’ skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients’ phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma.
2023-10-30 | GSE237986 | GEO
Project description:Filaggrin-2 (FLG2), a member of the S100-fused type protein family, is a 250 kDa protein mainly expressed in differentiated keratinocytes of the epidermis (Wu et al., 2009; Hsu et al., 2011). Its expression is reduced in atopic dermatitis (Pellerin et al., 2013), and heterozygous non-sense mutations of its gene are associated with a more persistent form of the disease in Afro-American populations (Margolis et al., 2014). Homozygous mutations of its gene are responsible for a rare skin disease called peeling skin syndrome type A (Bolling et al., 2018; Mohamad et al., 2018). However, the exact role of FLG2, a multi-domain protein, is not well known. Its COOH-tail exhibits anti-microbial activity (Hansmann et al., 2015), whereas its B domain is suspected to be involved in the hydration of the upper part of the epidermis, the cornified layer. Here, on the basis of immunological, global proteomics and in vitro enzymatic analysis we demonstrated that its amino-terminal domain is cross-linked to the cornified envelope, a pericellular resistant structure that replaces the plasma membrane during the last step of keratinocyte differentiation. In addition, depletion of FLG2 in reconstructed 3D human epidermis induced a marked fragility of cornified envelopes. These data suggest that FLG2 is important for proper mechanical strength of the cornified layer. They may explain the epidermal fragility observed in peeling skin syndrome type A patients.
2019-02-25 | PXD011833 | Pride
Project description:The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity – nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed fragile nucleosomes throughout the yeast genome, nearly one thousand of which are at previously determined “nucleosome free” loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization.
2011-01-24 | GSE26412 | GEO
Project description:Ageing compromises the mechanical properties of skin, with increased fragility and coincident slowing of the healing process making aged skin susceptible to chronic wounding. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, compounded by regulatory changes, including age-associated hormonal dysregulation. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and chronologically aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing lead to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the ovariectomy model was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, indicative of the role of estrogen-related pathways in ageing. This study offers a coherent picture of the relationship between tissue composition and mechanics, but suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.
2019-03-11 | PXD012753 | Pride
Project description:Ageing compromises the mechanical properties of skin, with increased fragility and coincident slowing of the healing process making aged skin susceptible to chronic wounding. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, compounded by regulatory changes, including age-associated hormonal dysregulation. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and chronologically aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing lead to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the ovariectomy model was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, indicative of the role of estrogen-related pathways in ageing. This study offers a coherent picture of the relationship between tissue composition and mechanics, but suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.
2019-03-11 | PXD012754 | Pride
Project description:Recessive dystrophic epidermolysis bullosa (RDEB) is a severely debilitating disorder caused by mutations in COL7A1 and is characterized by extreme skin fragility, chronic inflammation and fibrosis. A majority of RDEB patients develop squamous cell carcinoma (SCC), a highly aggressive skin cancer with limited treatment options currently available. In this study, we utilized a novel approach leveraging WGS and RNA-seq across three different tissues in a single RDEB patient to gain insight into possible mechanisms of RDEB-associated SCC progression and to identify potential novel therapeutic options. As a result, we identified PLK-1 as a possible candidate for targeted therapy and discovered microsatellite instability and accelerated aging as factors potentially contributing to the aggressive nature and early onset of RDEB SCC.
2024-02-17 | GSE236849 | GEO
Project description:Regulatory T cells (Tregs) are a barrier to effective anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune homeostasis, Treg-restricted Nrp1 deletion in mice results in profound tumor resistant due to Treg functional fragility. Drivers of Treg fragility, the mechanistic basis of Nrp1 dependency, and the relevance of these processes for human cancer and immunotherapy remain unknown. NRP1 expression on human Tregs in melanoma and HNSCC was highly heterogeneous and correlated with prognosis. Using a mouse model of melanoma in which mutant Nrp1-deficient (Nrp1–/–) and wild type (WT) Tregs could be assessed in a competitive environment, we found that a high proportion of intratumoral Nrp1–/– Tregs produce interferon-γ (IFNγ), which in turn drove the fragility of surrounding WT Tregs, boosting anti-tumor immunity and facilitating tumor clearance. We also show that IFNγ-induced Treg fragility is required for an effective response to PD1 immunotherapy, suggesting that cancer therapies promoting Treg fragility may be efficacious .
2017-05-22 | GSE97939 | GEO
Project description:CIDR_Genetic Determinants of Bone Fragility
| PRJNA75697 | ENA