The lineage of the horizontal basal cells (HBC) stem cells and other Sox2eGFP-positive cells from the olfactory epithelium were profiled by single-cell RNA-Seq to identify differentiated cells types, intermediate stages, transition states, and to infer the lineage trajectories. Overall design: Horizontal basal cell (HBC) stem cells from the olfactory epithelium that were either wild-type or mutant for the transcription factor Trp63/p63 were lineage traced, collected by FACS, and profiled by single-cell RNA-seq. Additionally, Sox2eGFP transgenic cells from the olfactory epithelium were combined with this data into one data set that was processed together. A minimum of two biological replicates were collected for each time-point/experimental condition. A total of 680 YFP-positive lineage traced cells plus 169 Sox2eGFP-positive cells were used in this analysis.
Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.
Subject
View SamplesNMuMG is an epithelial cell line that can be induced into EMT by TGF- treatment or MET by TGF- withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype.
Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin β4.
Cell line, Treatment
View SamplesPurpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 158 TN tumors (54 AA) from The Cancer Genome Atlas (TCGA). Meta-analyses were performed to obtain summary estimates by combining TCGA and Detroit AA cohort results. Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR)=1.56, 95% confidence interval (CI) 1.31-1.86, nominal p=5.1x10-7, FDR p=0.014], SPIC [HR=1.47, 95%CI 1.26-1.73, nominal p=1.8x10-6, FDR p=0.022], and MIR4311 [HR=1.57, 95% CI 1.31-1.92, nominal p=2.5x10-5, FDR p=0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. Meta-analysis with TCGA data showed that CLCA2 and SPIC were associated with overall survival for TNBC among AA women. Conclusions: We identified three potential prognostic markers for TNBC in AA women, for which SPIC may be an AA-specific prognostic marker.
CLCA2 expression is associated with survival among African American women with triple negative breast cancer.
Age, Treatment, Race
View SamplesCutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to investigate the transcriptomes of cSCC and actinic keratoses (AK), to elucidate key differences between precursor AK lesions and invasive carcinoma.
Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling.
Sex, Specimen part, Subject
View SamplesWe compared the transcriptome at gene expression level in hypoxic and normoxic conditions.
Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels.
Cell line, Treatment, Time
View SamplesCD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens. Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.
Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
Specimen part
View SamplesMice have been treated with NOX-A12. Whole BM cells have been harvested, RNA isolated, and gene expression profiling was performed on cDNA using Mouse Genome 430 2.0 array. Untreated mice have been used as control.
SDF-1 inhibition targets the bone marrow niche for cancer therapy.
Treatment
View SamplesEstrogen receptor a (ERa) is an important biomarker of breast cancer severity and a common therapeutic target. Recent studies have demonstrated that in addition to its role in promoting proliferation, ERa also protects tumors against metastatic transformation. Current therapeutics antagonize ERa and interfere with both beneficial and detrimental signaling pathways stimulated by ERa. The goal of this study is to uncover the dynamics of coding and non-coding RNA (microRNA) expression in response to estrogen stimulation and identify potential therapeutic targets that more specifically inhibit ERa-stimulated growth and survival pathways without interfering with its protective features. To achieve this, we exposed MCF7 cells (an estrogen receptor positive model cell line for breast cancer) to estrogen and prepared a time course of paired mRNA and miRNA sequencing libraries at ten time points throughout the first 24 hours of the response to estrogen. From these data, we identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of paired mRNA and microRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that over-expression of miR-503 suppresses breast cancer cell proliferation. Overall, these data indicate that miR-503 acts as a potent estrogen-induced tumor suppressor microRNA that opposes cellular proliferation and has promise as a therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. Overall design: Quantification of mRNAs in MCF7 cells responding to estrogen following a period of estrogen starvation. Three independent biological replicates (30 samples: 3 replicates x 10 time points) of MCF7 cells were exposed to 10nM Estradiol for 0, 1, 2, 3, 4, 5, 6, 8, 12 , or 24 hours, and total RNA was extracted from the samples. Total RNA was used to generate paired RNA and miRNA sequencing. RNA libraries were prepared using an Illumina TruSeq stranded mRNA library preparation kit.
An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells.
No sample metadata fields
View SamplesAE-expressing murine BM cells treated with all-trans retinoic acid (ATRA) in semi-solid methycellulose-based cultures show an increase in self-renewal capacity whilst treatment with a specific RARa agonist NRX195183 reduces their clonogenicity. Gene expression analysis was performed to further investigate the molecular mechanisms underlying these observations. Upregulated gene sets were identified in the ATRA-treated AE BM cells.
ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.
Specimen part, Treatment
View SamplesGlobal gene experssion study of the HAEC transcriptional response to artificial chlyomicron remnant-like particles (A-CRLPs) prepared with triglycerides extracted from four natural dietary oils: fish, DHASCO, corn and palm oils. We hypothesised that A-CRLPs could differentially regulate HAEC gene expression according to thier triglyceride content. These data provide an important starting point for investigations into the effects of A-CRLPs on endothelial cells, particulary genes involved in redox balance and inflammatory processes.
Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.
Specimen part
View Samples