Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1165399 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mutations in the RMRP gene are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in the RMRP gene lead to skeletal dysplasia. Viperin is a known substrate of RMRP. Since chondrogenic differentiation of the growth plate is required for development of the long bones, we hypothesized that viperin functions as a chondrogenic regulator downstream of RMRP. Viperin protein is expressed throughout the stages of chondrogenic differentiation in vivo. Viperin gene expression is increased during knockdown of Rmrp RNA in the ATDC5 model for chondrogenic differentiation. Viperin is expressed during ATDC5 chondrogenic differentiation. Viperin knockdown reduces, while viperin overexpression increases overall protein secretion, with CXCL10 identified as a potential target via mass spectrometry-proteomics. CXCL10 protein expression is reduced during knockdown and increased during overexpression of viperin and CXCL10 protein expression coincides with viperin expression in ATDC5 chondrogenic differentiation. Viperin knockdown induces, while viperin overexpression reduces TGFβ activity. Furthermore, viperin knockdown conditioned media increases, while viperin overexpression conditioned media reduces chondrogenic differentiation of ATDC5 cells. TGFβ target genes Pai1 and Smad7 are increased during knockdown and reduced during overexpression of viperin. Moreover, TGFβ activity is reduced when differentiating ATDC5 cells are exposed to CXCL10 and, acting as a viperin overexpression mimic, CXCL10 similarly reduces chondrogenic differentiation of ATDC5. Lastly, we show that in CHH patient cells, RMRP expression is reduced and viperin expression is increased, coinciding with reduced chondrogenic differentiation and increased CXCL10 expression, possibly explaining the CHH phenotype. Together our data show that viperin may play a pivotal role in chondrogenic differentiation, with potential consequences for cartilage-hair hypoplasia pathobiology.
2019-02-15 | PXD006999 | Pride
Project description:We used primary human CHH (cartilage-hair hypoplasia) and control fibroblasts in a chondrogenic transdifferentiation model (FDC; fibroblast-derived chondrocytes) to determine the chondrogenic capacity and differential pathway regulation of CHH cells. For the sequencing experiment, dermal fibroblasts from control donors (n=4) and CHH patients (n=4) were isolated from skin biopsies, plated at high density into wells coated with aggrecan, and cultured for three days in an FDC transdifferentiation medium. Total RNA was isolated at three different time points (Day 0, 1, and 3; in total 24 RNA samples), and sequenced using the NextSeq platform (Illumina).
2021-10-09 | E-MTAB-10996 | biostudies-arrayexpress
Project description:Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most severe congenital heart defect encompassing a spectrum of left-ventricular hypoplasia occurring in association with outflow-tract obstruction. The current clinical paradigm assumes HLHS is largely of hemodynamic origin. Here, by combining whole-exome sequencing of 87 HLHS parent-offspring trios and transcriptome of cardiomycytes (CMs) from healthy and patient native ventricles at different stages of development we identified perturbations in coherent gene programs controlling ventricular muscle lineage development. Single-cell and 3D molecular/functional modeling with iPSCs demonstrated intrinsic defects in the cell-cycle/ciliogenesis/autophagy hub resulting in disrupted differentiation of early cardiac progenitor (CP) lineages and ultimate defective CM-subtype differentiation/maturation in HLHS. Moreover, premature cellcycle exit of ventricular CM prevents tissue response to cues of developmental growth leading to multinucleation/polyploidy, accumulation of DNA damage, exacerbated apoptosis, and eventually ventricle hypoplasia. Our results highlight how genetic heterogeneity in HLHS converges in perturbations of sequential cellular processes driving cardiogenesis and facilitate potential novel nodes for therapy beside surgical intervention.
2022-02-15 | PXD014812 | Pride
Project description:Transcriptomic analysis of cartilage-hair hypoplasia (CHH) patients compared to controls, using the STRT sequencing method.
| PRJEB23608 | ENA
Project description:RNA-seq of control and CHH (cartilage-hair hypoplasia) fibroblasts transdifferentiated into chondrocytes-like cells
| PRJEB47817 | ENA
Project description:Purpose: There are three goals of this study: 1. To compare the genomic, exome and chromatin accessiblity profiles of the specific engineered fallopian tube cells of high-grade serous tubo-ovarian cancer (HGSC) models (this study) using whole-exome, whole-genome and ATAC-seq sequencing. Methods: For whole-exome analysis, genomic DNA was extracted from the cell lines mentioned below. Conclusions: We conclude that whole-exome, whole-genome and ATAC-seq characterization would expedite genetic network analyses and permit the dissection of complex biological functions.
2020-11-17 | GSE159253 | GEO
Project description:Agilent whole exome hybridisation capture was performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. Now we aim to re find and validate the findings of those exome libraries using bespoke pulldown methods and sequencing the products.
2016-05-17 | E-ERAD-37 | biostudies-arrayexpress
Project description:TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.
2022-02-16 | PXD023584 | Pride
Project description:Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage–hair hypoplasia
| PRJNA219492 | ENA
Project description:Paired end whole exome sequencing for patient 10, matched normal and tumor
2020-02-01 | E-MTAB-8127 | biostudies-arrayexpress