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Article ; Online: Discovery of a previously unreported deletion in the CDKN2A gene in a case of familial melanoma in Austria.

Okamoto, Ichiro / Pfisterer, Karin / Wielscher, Matthias / Weninger, Wolfgang

European journal of cancer (Oxford, England : 1990)

2022 Volume 181, Page(s) 21–22

MeSH term(s)	Humans ; Genes, p16 ; Austria ; Melanoma/genetics ; Skin Neoplasms/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Germ-Line Mutation ; Gene Deletion ; Melanoma, Cutaneous Malignant
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; CDKN2A protein, human
Language	English
Publishing date	2022-12-09
Publishing country	England
Document type	Case Reports ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2022.11.037
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Zs.MO 583: Show issues

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Article: Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study.

Sunder-Plassmann, Raute / Geusau, Alexandra / Endler, Georg / Weninger, Wolfgang / Wielscher, Matthias

Cancers

2023 Volume 15, Issue 13

Abstract: Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients ( ...

Abstract	Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (
Language	English
Publishing date	2023-06-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133354
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Article ; Online: Impact of the COVID-19 pandemic on the epidemiology of severe burns : A single center study from a specialized burn center in Vienna.

Christ, Alexandra / Staud, Clement J / Wielscher, Matthias / Resch, Annika / Teufelsbauer, Maryana / Radtke, Christine

Wiener klinische Wochenschrift

2023 Volume 135, Issue 9-10, Page(s) 244–250

Abstract: Introduction: Currently, very little detailed information on the epidemiological distribution and specificities of severely burned patients during the coronavirus disease 2019 (COVID-19) pandemic is available. This retrospective study aims to describe ... ...

Abstract	Introduction: Currently, very little detailed information on the epidemiological distribution and specificities of severely burned patients during the coronavirus disease 2019 (COVID-19) pandemic is available. This retrospective study aims to describe and compare this specific patient population based on 114 patients who were treated between March 2019 and March 2021 at the Center for Severe Burn Injuries at the Medical University of Vienna. Methods: To answer the research questions, a retrospective cohort study has been conducted over a period of 24 months, starting in March 2019 and ending in March 2021. To evaluate the epidemiological differences, the patients were divided into 2 observation periods of 12 months each. Results: In the period from 12 March 2020 to 11 March 2021, a total of 62 patients were admitted to the Center for Severe Burn Injuries. In comparison, only 52 patients were admitted in the same period of the previous year, which corresponds to an increase of 19.2%. In addition, it was noted that during the 2019-2020 observation period, 27% of patients were female and 73% male, whereas during the pandemic the gender distribution was 42% female and only 58% male. During the pre-pandemic observational period, 13 out of 52 patients admitted died (25%), whereas during the pandemic, 17 out of 62 patients succumbed to their injuries (27%). Conclusion: Although the severity of the COVID-19 pandemic seems to be decreasing, especially due to the increasing availability of vaccines, there is a need for more data on the impact of the crisis on severely burned patients. In contrast to the current literature, we have seen a greater number of inpatient admissions to the Center for Severe Burn Injuries, as well as significant differences in gender distribution. Our data also suggest that the circumstances of the pandemic have no influence on the likelihood of survival for patients with severe burns.
MeSH term(s)	Humans ; Male ; Female ; Burn Units ; Retrospective Studies ; Length of Stay ; Pandemics ; COVID-19/epidemiology
Language	English
Publishing date	2023-02-09
Publishing country	Austria
Document type	Journal Article
ZDB-ID	200462-8
ISSN	1613-7671 ; 0043-5325 ; 0300-5178
ISSN (online)	1613-7671
ISSN	0043-5325 ; 0300-5178
DOI	10.1007/s00508-022-02149-1
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Article ; Online: Single-cell transcriptomics defines keratinocyte differentiation in avian scutate scales.

Lachner, Julia / Ehrlich, Florian / Wielscher, Matthias / Farlik, Matthias / Hermann, Marcela / Tschachler, Erwin / Eckhart, Leopold

Scientific reports

2022 Volume 12, Issue 1, Page(s) 126

Abstract: The growth of skin appendages, such as hair, feathers and scales, depends on terminal differentiation of epidermal keratinocytes. Here, we investigated keratinocyte differentiation in avian scutate scales. Cells were isolated from the skin on the legs of ...

Abstract	The growth of skin appendages, such as hair, feathers and scales, depends on terminal differentiation of epidermal keratinocytes. Here, we investigated keratinocyte differentiation in avian scutate scales. Cells were isolated from the skin on the legs of 1-day old chicks and subjected to single-cell transcriptomics. We identified two distinct populations of differentiated keratinocytes. The first population was characterized by mRNAs encoding cysteine-rich keratins and corneous beta-proteins (CBPs), also known as beta-keratins, of the scale type, indicating that these cells form hard scales. The second population of differentiated keratinocytes contained mRNAs encoding cysteine-poor keratins and keratinocyte-type CBPs, suggesting that these cells form the soft interscale epidermis. We raised an antibody against keratin 9-like cysteine-rich 2 (KRT9LC2), which is encoded by an mRNA enriched in the first keratinocyte population. Immunostaining confirmed expression of KRT9LC2 in the suprabasal epidermal layers of scutate scales but not in interscale epidermis. Keratinocyte differentiation in chicken leg skin resembled that in human skin with regard to the transcriptional upregulation of epidermal differentiation complex genes and genes involved in lipid metabolism and transport. In conclusion, this study defines gene expression programs that build scutate scales and interscale epidermis of birds and reveals evolutionarily conserved keratinocyte differentiation genes.
MeSH term(s)	Animal Scales/cytology ; Animal Scales/metabolism ; Animals ; Animals, Newborn ; Avian Proteins/genetics ; Avian Proteins/metabolism ; Cell Differentiation/genetics ; Chickens/genetics ; Chickens/metabolism ; Evolution, Molecular ; Extremities ; Gene Expression Profiling ; Keratinocytes/metabolism ; RNA-Seq ; Single-Cell Analysis ; Species Specificity ; Transcription, Genetic ; Transcriptome
Chemical Substances	Avian Proteins
Language	English
Publishing date	2022-01-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-04082-1
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Article ; Online: Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8

Kamnev, Anton / Mehta, Tanvi / Wielscher, Matthias / Chaves, Beatriz / Lacouture, Claire / Mautner, Anna-Katharina / Shaw, Lisa E / Caldera, Michael / Menche, Jörg / Weninger, Wolfgang P / Farlik, Matthias / Boztug, Kaan / Dupré, Loïc

Cell reports

2024 Volume 43, Issue 3, Page(s) 113853

Abstract: Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human ... ...

Abstract	Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human CD8
MeSH term(s)	Humans ; Actins/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Interleukin-2/metabolism ; Actin Cytoskeleton/metabolism ; Actin-Related Protein 2-3 Complex/metabolism
Chemical Substances	Actins ; Interleukin-2 ; Actin-Related Protein 2-3 Complex
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113853
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Article: Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients.

Pfisterer, Karin / Wielscher, Matthias / Samardzic, David / Weinzettl, Pauline / Symmank, Dorte / Shaw, Lisa E / Campana, Raffaela / Huang, Huey-Jy / Farlik, Matthias / Bangert, Christine / Vrtala, Susanne / Valenta, Rudolf / Weninger, Wolfgang

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1240289

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 cytokine-driven skin inflammation and epithelial barrier dysfunction. The latter is believed to allow the increased penetration of chemicals, toxins, and allergens into ...

Abstract	Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 cytokine-driven skin inflammation and epithelial barrier dysfunction. The latter is believed to allow the increased penetration of chemicals, toxins, and allergens into the skin. House dust mite allergens, particularly Der p 2, are important triggers in sensitized individuals with AD; the precise actions of these allergens in epithelial biology remain, however, incompletely understood. In this study, we compared the effects of the protein allergen Der p 2 and a mix of non-IgE-reactive Der p 2 peptides on skin cells using patch tests in AD patients and healthy participants. We then analyzed mRNA expression profiles of keratinocytes by single-cell RNA-sequencing. We report that existing barrier deficiencies in the non-lesional skin of AD patients allow deep penetration of Der p 2 and its peptides, leading to local microinflammation. Der p 2 protein specifically upregulated genes involved in the innate immune system, stress, and danger signals in suprabasal KC. Der p 2 peptides further downregulated skin barrier genes, in particular the expression of genes involved in cell-matrix and cell-cell adhesion. Peptides also induced genes involved in hyperproliferation and caused disturbances in keratinocyte differentiation. Furthermore, inflammasome-relevant genes and IL18 were overexpressed, while KRT1 was downregulated. Our data suggest that Der p 2 peptides contribute to AD initiation and exacerbation by augmenting hallmark features of AD, such as skin inflammation, barrier disruption, and hyperplasia of keratinocytes.
Language	English
Publishing date	2023-08-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1240289
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Article ; Online: The transcriptional profile of keloidal Schwann cells.

Direder, Martin / Wielscher, Matthias / Weiss, Tamara / Laggner, Maria / Copic, Dragan / Klas, Katharina / Bormann, Daniel / Vorstandlechner, Vera / Tschachler, Erwin / Jan Ankersmit, Hendrik / Mildner, Michael

Experimental & molecular medicine

2022 Volume 54, Issue 11, Page(s) 1886–1900

Abstract: Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, ... ...

Abstract	Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-022-00874-1
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Zs.A 4775: Show issues

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Article ; Online: Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment.

Wielscher, Matthias / Amaral, Andre F S / van der Plaat, Diana / Wain, Louise V / Sebert, Sylvain / Mosen-Ansorena, David / Auvinen, Juha / Herzig, Karl-Heinz / Dehghan, Abbas / Jarvis, Debbie L / Jarvelin, Marjo-Riitta

Genome medicine

2021 Volume 13, Issue 1, Page(s) 104

Abstract: Background: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by ... ...

Abstract	Background: Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors. Methods: We performed three analyses: (1) cardio-metabolic health to lung function association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) to compare genetic backgrounds and (3) Mendelian randomisation (MR) analysis to assess the causal effect of cardio-metabolic traits and disease on lung function, and vice versa (bidirectional MR). Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies (N > 82,000). Results: We observed a negative genetic correlation between lung function and cardio-metabolic traits and diseases. In Mendelian Randomisation analysis (MR), we found associations between type 2 diabetes (T2D) instruments and forced vital capacity (FVC) as well as FEV1/FVC. Body mass index (BMI) instruments were associated to all lung function traits and C-reactive protein (CRP) instruments to FVC. These genetic associations provide evidence for a causal effect of cardio-metabolic traits on lung function. Multivariable MR suggested independence of these causal effects from other tested cardio-metabolic traits and diseases. Analysis of lung function specific SNPs revealed a potential causal effect of FEV1/FVC on blood pressure. Conclusions: The present study overcomes many limitations of observational studies by using Mendelian Randomisation. We provide evidence for an independent causal effect of T2D, CRP and BMI on lung function with some of the T2D effect on lung function being attributed to inflammatory mechanisms. Furthermore, this analysis suggests a potential causal effect of FEV1/FVC on blood pressure. Our detailed analysis of the interplay between cardio-metabolic traits and impaired lung function provides the opportunity to improve the quality of existing intervention strategies.
MeSH term(s)	Biomarkers ; Body Mass Index ; Cardiometabolic Risk Factors ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/epidemiology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Disease Susceptibility ; Finland/epidemiology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Inflammation Mediators ; Linkage Disequilibrium ; Lung/metabolism ; Lung/physiopathology ; Lung Diseases/epidemiology ; Lung Diseases/etiology ; Metabolic Syndrome/complications ; Metabolic Syndrome/epidemiology ; Polymorphism, Single Nucleotide ; Public Health Surveillance ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Respiratory Function Tests ; Risk Assessment
Chemical Substances	Biomarkers ; Inflammation Mediators
Language	English
Publishing date	2021-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-021-00914-x
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Article ; Online: Single-Cell RNA Sequencing Reveals Tissue Compartment-Specific Plasticity of Mycosis Fungoides Tumor Cells.

Rindler, Katharina / Bauer, Wolfgang M / Jonak, Constanze / Wielscher, Matthias / Shaw, Lisa E / Rojahn, Thomas B / Thaler, Felix M / Porkert, Stefanie / Simonitsch-Klupp, Ingrid / Weninger, Wolfgang / Mayerhoefer, Marius E / Farlik, Matthias / Brunner, Patrick M

Frontiers in immunology

2021 Volume 12, Page(s) 666935

Abstract: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known ... ...

Abstract	Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (T
MeSH term(s)	Aged ; Antigens, CD/biosynthesis ; Antigens, CD/genetics ; Antigens, Neoplasm/biosynthesis ; Antigens, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunologic Memory ; Lymph Nodes/metabolism ; Mycosis Fungoides/genetics ; Mycosis Fungoides/metabolism ; Mycosis Fungoides/pathology ; Neoplastic Stem Cells/chemistry ; Neoplastic Stem Cells/pathology ; Sequence Analysis, RNA ; Skin/cytology ; Skin/immunology ; Skin Neoplasms/pathology ; T-Lymphocytes/chemistry ; T-Lymphocytes/pathology ; Tumor Microenvironment
Chemical Substances	Antigens, CD ; Antigens, Neoplasm
Language	English
Publishing date	2021-04-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.666935
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Article ; Online: Association of adult lung function with accelerated biological aging.

Rezwan, Faisal I / Imboden, Medea / Amaral, Andre F S / Wielscher, Matthias / Jeong, Ayoung / Triebner, Kai / Real, Francisco Gómez / Jarvelin, Marjo-Riitta / Jarvis, Deborah / Probst-Hensch, Nicole M / Holloway, John W

Aging

2020 Volume 12, Issue 1, Page(s) 518–542

Abstract: Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and ... ...

Abstract	Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10
MeSH term(s)	Adult ; Age Factors ; Aging/physiology ; Biomarkers ; Cross-Sectional Studies ; Epigenesis, Genetic ; Female ; Humans ; Lung/metabolism ; Lung/physiopathology ; Male ; Meta-Analysis as Topic ; Middle Aged ; Respiratory Function Tests ; Sex Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.102639
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