The purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs).
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Specimen part, Disease, Disease stage
View SamplesThe purpose of this study was to identify molecular markers of pathologic response to neoadjuvant dose-dense docetaxel treatment using gene expression profiling on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with 75 mg/m2 IV of docetaxel on day 1 of each cycle every 2 weeks x 4 cycles . Tumor tissue from pretreatment biopsies was obtained from 12 patients enrolled in the study. Gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR).
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Specimen part, Treatment
View SamplesFor most multigenic disorders, clinical manifestation (penetrance) and presentation (expressivity) are likely to be an outcome of genetic interaction between multiple susceptibility genes. Here, using gene knockouts in mice we evaluated genetic interaction between loss of Ret and loss of Sema3d, two Hirschsprung disease (HSCR) susceptibility genes. We intercrossed Ret and Sema3d double null heterozygotes to generate mice with the nine possible genotypes and assessed survival by counting various genotypes, myenteric plexus development by acetylcholinesterase (AchE) staining and embryonic day 12.5 (E12.5) gut transcriptome by RNA-sequencing. Survival rates of Ret wildtype, null heterozygote and null homozygote mice at E12.5, birth and weaning were not influenced by the genotypes at Sema3d locus and vice-versa. Loss of myenteric plexus was observed only in all Ret null homozygotes, irrespective of the genotypes at Sema3d locus, and Sema3d null heterozygote and homozygote mice had normal gut innervation. As compared to wildtype mice gut gene expression, loss of Ret in null homozygotes led to differential expression of ~300 genes, whereas loss of Sema3d in null homozygotes had no major consequence and there was no evidence supporting major interaction between the two genes influencing gut transcriptome. Overall, given the null alleles and phenotypic assays used, we did not find evidence for genetic interaction between Ret and Sema3d affecting survival, myenteric plexus formation or gut transcriptome. Overall design: poly-A RNA-seq in embryonic day 12.5 mouse gut from 3 wildtype males, 3 wildtype females, 3 Ret null homozyogote males, 3 Ret null homozyogote females, 3 Sema3d null homozyogote males, 3 Sema3d null homozyogote females, 3 Ret-Sema3d double null homozyogote males, 3 Ret-Sema3d double null homozyogote females
Testing the Ret and Sema3d genetic interaction in mouse enteric nervous system development.
Sex, Specimen part, Cell line, Subject
View SamplesTo elucidate biological processes underlying the keratocyte, fibroblast, and myofibroblast phenotypes of corneal stromal cells, the gene expression patterns of these primary cultures from mouse cornea were compared with those of the adult and 10-day postnatal mouse cornea.
Microarray studies reveal macrophage-like function of stromal keratocytes in the cornea.
No sample metadata fields
View SamplesThe cornea continues to mature after birth to develop a fully functional, refractive and protective barrier tissue. Here we investigated the complex biological events underlying this process by profiling global genome-wide gene expression patterns of the immature postnatal day 10 and seven week-old adult mouse cornea. The lens and tendon were included in the study to increase the specificity of genes identified as up regulated in the corneal samples. Notable similarities in gene expression between the cornea and the tendon were in the mesenchymal extracellular matrix collagen (types I, III, V, VI) and proteoglycan (lumican, decorin and biglycan) genes. Expression similarities in the cornea and lens were limited to certain epithelial genes and the crystallins. Approximately 76 genes were over expressed in the cornea samples that showed basal expression levels in the lens and tendon. Thirty-two of these were novel with no known functions in the cornea. These include genes with a potential role in protection against oxidative stress (Dhcr24, Cdo1, Akr1b7, Prdx6), inflammation (Ltb4dh, Wdr1), ion-transport (Pdzk1ip1, Slc12a2, Slc25a17) and transcription (Zfp36l3, Pdzk1ip1). Direct comparison of the cornea of two ages showed selective up regulation of 50 and 12 genes in the P10 and adult cornea, respectively. Of the up regulated P10 genes several encode extracellular matrix collagens and proteoglycans that are stable components of the adult cornea and their high transcriptional activity at P10 indicate a period of active corneal growth and matrix deposition in the young cornea. Much less is known about the genes selectively over expressed in the adult cornea; some relate to immune response and innervations (Npy), and possibly to electron transport (Cyp24a1, Cyp2f2) and others of yet unknown functions in the cornea (Rgs10, Psmb8, Xlr4)). This study detected expression of genes with known functions in the cornea, providing additional validation of the microarray experiments. Importantly, it identified several novel genes whose functions have not been investigated in the cornea.
Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon.
No sample metadata fields
View SamplesWe observed inhibition of the hypersensitive response (a typical ETI response) by PTI signaling in an Arabidopsis quadruple mutant dde2 ein2 pad4 sid2 (quad). Thus, we designed an experiment to see the interaction between ETI and PTI signaling at the transcriptome level. The Arabidopsis line dde2 ein2 pad4 sid2 Ed-AvrRpt2 (quadAvrRpt2) was used (Ed-AvrRpt2, estradiol-inducible AvrRpt2 transgene). In this plant line, ETI can be elicited by estradiol (Ed) treatment via in planta expression of AvrRpt2. Transcriptome responses to PTI only, ETI only, and PTI+ETI together were recorded. Overall design: quadAvrRpt2 was treated with one of (1) Mock, (2) flg22 to elicit PTI response only, (3) Ed to elicit ETI response only via AvrRpt2, (4) flg22+Ed to elicit both PTI and ETI responses together. At 0 (untouched), 60, 120, 180, and 300 minutes after treatment, treated plant leaves were harvested for RNA-seq analysis. Three independent experiments were performed (rep1-rep3).
A plant effector-triggered immunity signaling sector is inhibited by pattern-triggered immunity.
Specimen part, Treatment, Subject
View SamplesIt is becoming better understood that radiation resistance in glioblastomas (GBMs) may be secondary to a self-renewing subpopulation of cells in the bulk tumor that form neurospheres in culture. This population has been referred to as Glioma stem cells (GSCs). One of the limitations regarding the use of GSCs is that these studies require fresh tumor biopsy samples obtained from patients, and can be extremely difficult to culture, propagate, and perform treatment-response assays. This report describes the generation of a self-renewing population of GSCs derived from commercially available U87 cells using NOD-SCID mice as carrier. The tumors were dissociated to obtain GSCs that demonstrate stem-like properties and high degree of chemo and radiation resistance. Pathological analysis of tumors obtained using GSCs exhibit all the histological hallmarks of human GBMs which is quite uncommon in GBM rodent models and hence could serve as a better model for pre-clinical study. We have shown that MGH87GSCs have an enhanced tumorogenicity than parental U87 and about 500 cells are sufficient to form tumors. To understand the transcriptome and accompanied proteome better, we explored the gene expression profiles of MGH87GSC and U87. We have shown that these GSCs are plastic like stem cells and can be directed towards a particular progeny within neural lineage by providing suitable growth factor. Our objective was to understand the genetic and biochemical mechanisms that control the self-renewal phenotype, asymmetric subdivision, chemo and radiation resistance and the role of the GSC niche in regulating the biological properties of GSC. Through this model we anticipate to devise therapeutic strategies to target this sub population of GSCs within GBMs to eradicate treatment resistance and tumor recurrence.
Cells isolated from residual intracranial tumors after treatment express iPSC genes and possess neural lineage differentiation plasticity.
Specimen part, Cell line
View SamplesRNA seq analyses were performed in granulosa cells (GCs) collected from gonadotropin treated ESR2 mutant rats. Data obtained from a null mutant with Esr2 exon 3 deletion (?3) and another DNA binding domain (DBD) mutant with exon 4 deletion (?4) were compared to that of wildtype (WT) rats. The raw data were analyzed using CLC genomics workbench. High quality RNA-sequencing reads were aligned to the Rattus norvegicus genome. Differentially expressed genes in ?3 or ?4 Esr2-mutant GCs were identified based on the following criteria: FDR p-Value =0.05 and an absolute fold change of 2. Fewer differentially expressed genes were identified in ?3 compared to the ?4 mutant group. As both of the mutant groups demonstrated a common phenotype of ovulation failure, differentially expressed genes common to both in ?3 and ?4 mutant rats were emphasized and further analyzed in the companion article “ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation” (Khristi et al., 2018).
ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation.
No sample metadata fields
View SamplesTotal mRNA seq was perfomed on widtype and Ret null mouse embryonic gut at 2 stages of devlopment- E11.5 and E12.5 Overall design: Total RNA from 3 replicates each of wildtype and Ret null emryonic gut was converted to cDNA and run on HiSeq 2000 (75 bp paired end)
Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease.
Cell line, Subject
View SamplesUlcerative colitis (UC) and Crohns disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies to estabolish 36 expression profiles, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls.
Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.
No sample metadata fields
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