Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA846598 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human fibroblasts from a control or a patient with compound heterozygous variants in KIAA0753 treated with SAG or WNT3A to test responses within canonical Hedgehog or WNT signaling.
2021-08-24 | GSE182286 | GEO
Project description:Purpose: Our single-cell RNAseq data show that LTBP2 is a marker of a cancer associated fibroblast subpopulation in colorectal cancer liver metastases. Moreover, MTT assays of cultured fibroblasts treated with anti-LTBP2 antibodies suggest that LTBP2 is essential for their survival. The goal of this study is to understand the role of LTBP2 in fibroblasts. Methods: Normal olon fibroblasts (CCD18Co) were transfected 48h with siRNA containing an anti-LTBP2 or a non target sequence. Cell monolayer total RNA of 3 biological replicates was then extracted and submitted to Illumina RNAseq using NovaSeq6000. Results: Transcriptomics revealed massive changes in gene expression when LTBP2 is knocked down: 496 genes were differentially expressed between the colon fibroblasts treated with siRNA anti-LTBP2 and NT. Those genes are implicated in diverse biological processes such as extracellular matrix organization, angiogenesis or cell adhesion. Conclusions: Our study explored LTBP2 functions in normal fibroblasts. RNAseq data support its important role. After 48h, LTBP2 silencing induces changes in gene expression of numerous genes involved in fibroblast functions.
2022-11-22 | GSE191323 | GEO
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE111394 | GEO
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE131322 | GEO
Project description:The dataset comprises of seven samples described below
1. Muscle samples from three patients with late-onset PEO caused by compound heterozygous POLG variants
M0305 POLG W748S/R1096C
M1105 POLG A467T/T251I+P587L
M1804 POLG A467T/X1240G+35aa
2. Muscle sample from a patient with adPEO with heterozygous TWNK variants
M0230 TWNK p.Arg357Pro
3. Blood control samples from two patients with late-onset PEO caused by compound heterozygous POLG variants
DNA2012-1630_S1 POLG W748S/R1096C
DNA2018-0168_S2 POLG A467T/T251I+P587L
4. Muscle samples from healthy control individuals
DNA2018-0172_S4 Healthy control 2
DNA2018-0173_S5 Healthy control 1
| EGAD00001004271 | EGA
Project description:Multi-locus imprinting Disturbances (MLID) are methylation defects affecting germline-derived Differentially Methylated Regions (gDMRs) and they have been associated with maternal-effect variants causing imprinting disorders in the offspring. In a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child without any features of imprinting disorders, novel compound heterozygous variants in the NLRP5 gene of the mother were found. Locus-specific and whole-genome methylation analysis by using Infinium MethylationEPIC BeadChip (WG-317-1001, Illumina) revealed MLID with different methylation profiles in both the siblings. The proband and the normal sibling were found to cluster with other MLID cases as shown by principal component analysis and unsupervised hierarchical clustering and remain distinct from controls. However, we were unable to cluster MLID cases associated with specific clinical phenotypes. The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID add further evidence to the role of NLRP5 in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals.
2019-10-01 | GSE133774 | GEO