Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes.
Mouse liver repopulation with hepatocytes generated from human fibroblasts.
Specimen part
View SamplesTo understand the population genetics of structural variants (SVs), and their effects on phenotypes, we developed an approach to mapping SVs, particularly transpositions, segregating in a sequenced population, and which avoids calling SVs directly. The evidence for a potential SV at a locus is indicated by variation in the counts of short-reads that map anomalously to the locus. These SV traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between an SV trait at one locus and genotypes at a distant locus indicate the origin and target of a transposition. Using ultra-low-coverage (0.3x) population sequence data from 488 recombinant inbred Arabidopsis genomes, we identified 6,502 segregating SVs. Remarkably, 25% of these were transpositions. Whilst many SVs cannot be delineated precisely, PCR validated 83% of 44 predicted transposition breakpoints. We show that specific SVs may be causative for quantitative trait loci for germination, fungal disease resistance and other phenotypes. Further we show that the phenotypic heritability attributable to sequence anomalies differs from, and in the case of time to germination and bolting, exceeds that due to standard genetic variation. Gene expression within SVs is also more likely to be silenced or dysregulated, as inferred from RNA-seq data collected from a subset of just over 200 of the MAGIC lines. This approach is generally applicable to large populations sequenced at low-coverage, and complements the prevalent strategy of SV discovery in fewer individuals sequenced at high coverage. Overall design: 209 samples consisting of different inbred lines from the Multiparent Advance Generation InterCross (MAGIC) population in the reference plant, Arabidopsis thaliana. For each sample, RNA was collected from the aerial shoot at the 4th true leaf stage, and Illumina mRNA-seq libraries were constructed (a single library was constructed with each line; that is, each MAGIC line is represented by one biological replicate). Using these libraries, which were non-stranded, paired-end 100 bp RNA-seq Illumina reads were generated for each sample, and used to quantify gene expresison in each MAGIC line. The resulting expression phenotypes are suitable for describing the impacts of genetic variation in the MAGIC line founders on the control of gene expression.
Genomic Rearrangements in <i>Arabidopsis</i> Considered as Quantitative Traits.
Subject
View SamplesPseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Existing experimental data in our lab showed significantly different levels of virulence of "early" and "late" P. aeruginosa infection isolates in a C. elegans slow killing model. We wished to examine the expression profile of these isolates in order to explore genes that may be responsible for the observed differences. The expression profiles of two pairs of isolates (four isolates in total) were compared to each other using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating virulence in these isolates. Data analysis was carried out using BIOCONDUCTOR software.
Modulation of gene expression by Pseudomonas aeruginosa during chronic infection in the adult cystic fibrosis lung.
No sample metadata fields
View SamplesPlant drought stress response and resistance are complex biological processes that merit systems-level analyses to dissect drought stress encountered by crops in the field. We have used gene expression profiling of Arabidopsis plants subjected to a controlled, sublethal, moderate drought (mDr) treatment to characterize early and late response to drought. We have also compared these profiles to those from plants treated with soil water deficit (progressive) drought (pDr) to reveal acclimation responses in plants.
Molecular and physiological analysis of drought stress in Arabidopsis reveals early responses leading to acclimation in plant growth.
Specimen part, Treatment
View SamplesWe aim to identify genes differentially expressed between mouse WT and COUP-TFI_Nex-Cre mutant cortices.
Postmitotic control of sensory area specification during neocortical development.
Specimen part
View SamplesClassification of tamixifen-treated breast cancer patients into high and low risk groups using the 76-gene signature
The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy.
No sample metadata fields
View SamplesWe report the transcriptome profile of one sequenced sample of mRNA isolated from pooled (20 from each genotype) abdomen fly extracts enriched in fat body content of fat body-specific Sdc RNAi knockdown and control flies Overall design: Abdominal fat body mRNA profiles of 4-6-day old control and fat body-specific Sdc RNAi knockdown were generated by deep sequencing using Illumina HiSeq 2500
Knockdown expression of Syndecan in the fat body impacts nutrient metabolism and the organismal response to environmental stresses in Drosophila melanogaster.
Subject
View SamplesIn order to understand the effect of genetic background on the response to gene dose perturbation, we performed mRNA transcriptional profiling on 99 hemizygotic lines (Df/+) from the DrosDel project, which have hybrid genetic background of OregonR/w1118. Overall design: We performed RNA-Seq analysis of 417 single adult flies in duplicate or triplicate. Flies are from 73 different genotypes. Differential gene expression was analyzed separately for each sex, gene expression from each genotype was compared to normalized mean of gene expression remaining 72 genotypes.
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sex, Subject
View SamplesWe performed mRNA transcriptional profiling on 99 hemizygotic lines (Df/+) from the DrosDel project covering 68% of chromosome 2L, in order to understand how changes in gene copy number affect overall transcriptome. Overall design: We performed RNA-Seq analysis on 396 pools of 15-25 adult flies each. Samples include males or females from 99 different genotypes in duplicate. Differential gene expression was analyzed separately for each sex, by comparing each genotype with the remaining 98.
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sex, Specimen part, Subject
View SamplesTo measure the response to gene dose, we performed mRNA-Seq of fly heads with molecularly defined deletions constructed from DrosDel deficiency lines (Ryder et al. Genetics 2007, 177(1):615-29) on the Illumina HiSeq 2000 platform. Overall design: We performed single-end next-generation sequencing (RNA-Seq) on poly-A+ RNA extracted from adult female and male heads in biological triplicate. Besides wildtype females (XX) and males (XY) that were heterozygous for deletions, we also sequenced females that were transformed into males (XX males) by using mutations in the sex determination gene transformer-2 (tra2). The original lines with deletions, including 22 deletions on the chromosome X and 12 deletions on the chromosome 3L, were from the DrosDel project. The diploid controls without DrosDel deletions were derived from w1118 (the parental line of DrosDel stocks) or Oregon-R Strain. We sequenced a total of 249 samples.
Dosage-Dependent Expression Variation Suppressed on the <i>Drosophila</i> Male <i>X</i> Chromosome.
Sex, Subject
View Samples