We have identified candidate genes from the Feml2 QTL influencing femur length through allele specific expression analysis of growth plates in C57BL/6J x CAST/EiJ F1 hybrids. This work provides the foundation to identify novel genes affecting bone geometry. Overall design: total RNA sequencing in 7 male C57BL/6JxCAST F1s
Genetic Dissection of a QTL Affecting Bone Geometry.
Sex, Age, Specimen part, Cell line, SubjectView Samples
The study looked at changes in gene expression profiles in subjects with Pulmonary Arterial Hypertension and Scleroderma (PAH-SSc) before and after treatment with Tadalafil. A total of ten subjects were enrolled and various clinical assessments including 6-minute walk tes, cardiac MRI and right heart catheterization were done in addition to gene expression study.
Changes in gene expression profiles in patients with pulmonary arterial hypertension associated with scleroderma treated with tadalafil.
Specimen part, Subject, TimeView Samples
The goal of this study was to assess whether the presence of HLA-B*35 contributes to activation of ER stress/UPR and inflammation in lcSScPAH PBMC.
The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.
Specimen partView Samples
Extracellular vesicles released from cultured H9 cells were fractionated by differential ultracentrifugation and their total RNA were isolated for microarray analysis.
Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells.
Specimen part, Cell lineView Samples
Despite much investigation, mechanisms conferring stage specific responsiveness of the corpus luteum (CL) to prostaglandin F2 (PG) are unknown. The objective of this study was to identify PG- induced changes in transcriptome of bovine CL specific to d 11 ( PG responsive) but not d 4 (PG refractory) CL associated with luteolysis. CL were collected from heifers at 0, 4 and 24 h following PG injection on d 4 and 11 of the estrous cycle (n = 5 animals/treatment) and isolated RNA labeled and hybridized to Affymetrix GeneChip Bovine Genome Arrays. At 4 and 24 h post PG respectively, 221 (d 4) and 661 (d 11) and 248 (d 4) and 1419 (d 11) regulated genes were identified.
Regulation of angiogenesis-related prostaglandin f2alpha-induced genes in the bovine corpus luteum.
Specimen part, TreatmentView Samples
We report the transcriptional response of the zebrafish digestive organs to an acute high-fat feed using RNASeq analysis and highlight the changes in gene expression involved in the synthesis, storage, and dispersal of lipids. These key physiological responses to a high-fat meal all stem from the endoplasmic reticulum (ER), where lipids are formed and assigned to their fates. Overall design: A feeding time course was undertaken with 6.5-dpf larval zebrafish. Triplicate samples were independently prepared from pairwise crosses fed either high-fat or low-fat food. 5% egg yolk emulsion (high-fat) feeds and 10% egg white (low-fat) feeds were prepared. At the appropriate time points, digestive organs (intestine, liver, pancreas) were dissected from 10 anesthetized larval zebrafish. Unfed controls were used to determine a transcriptional baseline.
Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.
No sample metadata fieldsView Samples
Bone mineral density (BMD) is a strong predictor of osteoporotic fracture. It is also one of the most heritable disease-associated quantitative traits. As a result, there has been considerable effort focused on dissecting its genetic basis. Here, we performed a genome-wide association study (GWAS) in a panel of inbred strains to identify associations influencing BMD. This analysis identified a significant (P=3.1 x 10-12) BMD locus on Chromosome firstname.lastname@example.org Mbp that replicated in two seperate inbred strain panels and overlapped a BMD quantitative trait locus (QTL) previously identified in a F2 intercross. The association mapped to a 300 Kbp region containing four genes; Gm2447, Gm20750, Cog6, and Lhfp. Â Further analysis found that Lipoma HMGIC Fusion Partner (Lhfp) was highly expressed in bone and osteoblasts and its expression was regulated by local expression QTL (eQTL) in multiple tissues. A co-expression network analysis revealed that Lhfp was strongly connected to genes involved in osteoblast differentiation. To directly evaluate its role in bone, Lhfp deficient mice (Lhfp-/-) were created using CRISPR/Cas9. Consistent with genetic and network predictions, bone marrow stromal cells (BMSCs) from Lhfp-/- displayed increased osteogenic differentiation. Lfhp-/- mice also had elevated BMD due to increased cortical bone mass. In conclusion, we used GWAS and systems genetics in mice to identify Lhfp as a regulator of osteoblast activity and bone mass. Overall design: Bones and osteoblast-derived from bone marrow stromal cells were profiles using RNA-seq from CC0016/GeniUnc mice (N=3 biological replicates per sample type)
Mouse genome-wide association and systems genetics identifies Lhfp as a regulator of bone mass.
Specimen part, Cell line, SubjectView Samples
Linkage analysis of complex traits in mice is a powerful tool to find loci affecting the phenotype but it has a poor resolution making it difficult to identify the underlying genes. We show here, using whole genome association analysis of gene expression traits in an outbred mouse population, the MF1 stock, that mapping resolution is greatly increased as compared to linkage. The fact that eQTLs discovered in other crosses were replicated and successfully mapped with high resolution in this population provides a strong proof of concept. In addition, we show that this population is a useful resource to resolve the eQTL hotspots detected in other studies. Finally, we highlight the importance of correcting for population structure in whole genome association studies in the outbred stock.
High-resolution mapping of gene expression using association in an outbred mouse stock.
No sample metadata fieldsView Samples
This SuperSeries is composed of the SubSeries listed below.
A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.
Sex, Specimen part, Disease, Disease stage, Treatment, SubjectView Samples