Correction: Winkler et al. The Adhesion G-Protein-Coupled Receptor GPR115/ Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1. 2022, , 3151.

In the original publication [...

Organoid Cultures In Silico: Tools or Toys?

The implementation of stem-cell-based organoid culture more than ten years ago started a development that created new avenues for diagnostic analyses and regenerative medicine. In parallel, computational modelling groups realized the potential of this culture system to support their theoretical approaches to study tissues in silico. These groups developed computational organoid models (COMs) that enabled testing consistency between cell biological data and developing theories of tissue self-organization.

The Adhesion G-Protein-Coupled Receptor GPR115/ Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1.

Among the 33 human adhesion G-protein-coupled receptors (aGPCRs), a unique subfamily of GPCRs, only , encoding GPR115, shows an obvious skin-dominated transcriptomic profile, but its expression and function in skin is largely unknown. Here, we report that GPR115 is present in a small subset of basal and in most suprabasal, noncornified keratinocytes of the stratified epidermis, supporting epidermal transcriptomic data. In psoriatic skin, characterized by hyperproliferation and delayed differentiation, the expression of GPR115 and KRT1/10, the fundamental suprabasal keratin dimer, is delayed.

Glyphosate differentially affects the allergic immune response across generations in mice.

Exposure to environmental pollutants via food, particularly during the prenatal and early postnatal periods, has been linked to adverse effects on the immune system. Among these pollutants, the widely used pesticide glyphosate has been associated with endocrine disruption, autism, and cancer. Occupational high exposure to glyphosate has also been shown to influence immune function and exacerbate allergic asthma.

To Detach, Migrate, Adhere, and Metastasize: CD97/ in Cancer.

Tumorigenesis is a multistep process, during which cells acquire a series of mutations that lead to unrestrained cell growth and proliferation, inhibition of cell differentiation, and evasion of cell death. Growing tumors stimulate angiogenesis, providing them with nutrients and oxygen. Ultimately, tumor cells invade the surrounding tissue and metastasize; a process responsible for about 90% of cancer-related deaths.

Adhesion GPCR GPR56 Expression Profiling in Human Tissues.

Despite the immense functional relevance of GPR56 (gene ) in highly diverse (patho)physiological processes such as tumorigenesis, immune regulation, and brain development, little is known about its exact tissue localization. Here, we validated antibodies for GPR56-specific binding using cells with tagged GPR56 or eliminated in immunotechniques. Using the most suitable antibody, we then established the human GPR56 tissue expression profile.

Epigenetic Drifts during Long-Term Intestinal Organoid Culture.

Organoids retain the morphological and molecular patterns of their tissue of origin, are self-organizing, relatively simple to handle and accessible to genetic engineering. Thus, they represent an optimal tool for studying the mechanisms of tissue maintenance and aging. Long-term expansion under standard growth conditions, however, is accompanied by changes in the growth pattern and kinetics.

How to Obtain a Mega-Intestine with Normal Morphology: In Silico Modelling of Postnatal Intestinal Growth in a Cd97-Transgenic Mouse.

Intestinal cylindrical growth peaks in mice a few weeks after birth, simultaneously with crypt fission activity. It nearly stops after weaning and cannot be reactivated later. Transgenic mice expressing / in the intestinal epithelium develop a mega-intestine with normal microscopic morphology in adult mice.

Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions.

VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants of cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency of is associated with epilepsy. However, its molecular function remains elusive.

Fighting Against Promoter DNA Hyper-Methylation: Protective Histone Modification Profiles of Stress-Resistant Intestinal Stem Cells.

Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Recently, we have suggested that promoter DNA hyper-methylation originates in DNA repair and that even successful DNA repair might confer this kind of epigenetic long-term change. Here, we ask for interrelations between promoter DNA methylation and histone modification changes observed in the intestine weeks after irradiation and/or following loss.

Recipient Hepatic Tumor-Associated Immunologic Infiltrates Predict Outcomes After Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND Transplantation of the liver entails a state of altered recipient immunologic competence. There are only scarce data concerning the impact of host immunologic factors on the outcome of liver transplant recipients in the context of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Our study focused on evaluating the presence of tumor necrosis and frequency levels of angiopoietins and monocytes/macrophages subtypes in the host liver prior to liver transplantation (LTX) and their association with recurrence, graft rejection, survival, and clinical prognosis after LTX.

Free cholesterol, cholesterol precursor and plant sterol levels in atherosclerotic plaques are independently associated with symptomatic advanced carotid artery stenosis.

Background And Aims: Circulating sterols result either from cholesterol (CH) synthesis or intestinal uptake. They are mainly esterified and can be oxygenated. Sterols accumulate in atherosclerotic plaques whereby their clinical impact is uncertain.

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis.

Background: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC).

Immunologic cellular characteristics of the tumour microenvironment of hepatocellular carcinoma drive patient outcomes.

Background: Anti-tumour immune competence has an impact in hepatocarcinogenesis and success of anti-cancer therapies. Tumour-infiltrating lymphocytes (TILs) and monocytes/macrophages (TAMs) are proposed to have significance in cancer. However, there is only limited data concerning their impact on patient outcome and survival in hepatocellular carcinoma (HCC).

The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors.

The adhesion class of G protein-coupled receptors (GPCRs) is the second largest family of GPCRs (33 members in humans). Adhesion GPCRs (aGPCRs) are defined by a large extracellular N-terminal region that is linked to a C-terminal seven transmembrane (7TM) domain via a GPCR-autoproteolysis inducing (GAIN) domain containing a GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at the GPS motif, but the cleaved fragments stay closely associated, with the N-terminal fragment (NTF) bound to the 7TM of the C-terminal fragment (CTF).

Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine.

Background: Mismatch repair (MMR)-deficiency increases the risk of colorectal tumorigenesis. To determine whether the tumors develop on a normal or disturbed epigenetic background and how radiation affects this, we quantified genome-wide histone H3 methylation profiles in macroscopic normal intestinal tissue of young radiated and untreated MMR-deficient VCMsh2 (Msh2) mice months before tumor onset.

Results: Histone H3 methylation increases in Msh2 compared to control Msh2 mice.

Mechano-Dependent Phosphorylation of the PDZ-Binding Motif of CD97/ADGRE5 Modulates Cellular Detachment.

Cells respond to mechanical stimuli with altered signaling networks. Here, we show that mechanical forces rapidly induce phosphorylation of CD97/ADGRE5 (pCD97) at its intracellular C-terminal PDZ-binding motif (PBM). Biochemically, this phosphorylation disrupts CD97 binding to PDZ domains of the scaffold protein DLG1.

TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas.

Introduction: M2-polarized tumor-associated macrophages (TAMs) and TIE2-expressing monocytes (TEMs) are associated with angiogenesis and have been identified as a potential prognostic marker in several solid tumors, including hepatobiliary malignancies. However, little is known regarding their influence on tumor progression and patient survival in pancreatic ductal adenocarcinoma (PDAC).

Results: Patients with tumors characterized by the presence of CD163 TAMs or TEMs in TCA or TIF, respectively, showed a significantly decreased 1-, 3- and 5-year overall and recurrence-free survival compared to patients without CD163 TAMs or TEMs (all < 0.

The Interaction of CD97/ADGRE5 With β-Catenin in Adherens Junctions Is Lost During Colorectal Carcinogenesis.

The adhesion G-protein-coupled receptor CD97/ADGRE5 is present in adherens junctions of human normal intestinal cells and upregulated in colorectal carcinomas. Here, we examined whether CD97 directly interacts with junctional proteins in normal and malignant colorectal tissue. We identified an association of CD97 with β-catenin using a proximity ligation assay and confirmed the interaction between both endogenous proteins at the biochemical level by co-immunoprecipitation in human and mouse tissues and cell lines.

Single-Stage Preparation of Human Cartilage Grafts Generated from Bone Marrow-Derived CD271 Mononuclear Cells.

Due to the limited self-healing capacity of articular cartilage, innovative, regenerative approaches are of particular interest. The use of two-stage procedures utilizing in vitro-expanded mesenchymal stromal cells (MSCs) from various cell sources requires good manufacturing practice-compliant production, a process with high demands on time, staffing, and financial resources. In contrast, one- stage procedures are directly available, but need a safe enrichment of potent MSCs.

Linking stem cell function and growth pattern of intestinal organoids.

Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture.

Functional and clinical relevance of novel and known variants for childhood obesity and glucose metabolism.

Objective: Variants in () may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known variants in children.

Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.