The data contains RNA sequencing data of embryonic stem cell derived cells.
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Sex, Specimen part, Cell line
View SamplesAims: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5’ splice site to an upstream 3’ splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts.[1,2] Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments.Methods and Results: Deep RNA sequencing of cardiomyocyte development and ß-adrenergic stimulation uncovered 4,518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intri-guingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes.Conclusion: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene inde-pendent expression dynamics in patient samples and may interact with the ribo-some and RISC complex. In summary, the hiPSC-CM model uncovered a new sig-nature of potentially disease relevant circRNAs which may serve as novel therapeu-tic targets.
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Sex, Specimen part, Race
View SamplesK562 single cell RNA-seq study
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View SamplesWe examined skin biopsies from a diverse cohort of 23 SSc patients (including lesional forearm and non-lesional back samples) by RNA-seq. Metagenomic filtering and annotation was performed using the Integrated Metagenomic Sequencing Analysis (IMSA). Associations between microbiome composition and gene expression were analyzed using single-sample gene set enrichment analysis (ssGSEA).
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Sex, Age, Specimen part
View SamplesEstrogens have been shown to elicit anti-cancer effects against estrogen receptor alpha (ER)-positive breast cancer. We sought to determine the underlying mechanism of therapeutic response. Response to estrogen treatment was assessed in ER+ breast cancer models of anti-estrogen resistant disease: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells.
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Sex, Age, Specimen part
View SamplesMicroenvironmental secreted factor screening revealed cytokines that modulate drug sensitivity in ER+ breast cancer cells. BMP4 was a top hit that is not normally expressed in ER+ breast cancer, and was found to enhance efficacy of anti-estrogens and CDK4/6i in anti-estrogen-sensitive and -resistant ER+ breast cancer cells. The anti-cancer effects of BMP4 were mediated by ALK3 and canonical BMP pathway signaling, leading to downstream p21 induction and cell cycle arrest. The clinical relevance of this phenotype was confirmed in analyses of 3 cohorts of patients with ER+ breast cancer, highlighting BMP4 pathway activation as a potential therapeutic opportunity in ER+ breast cancer.
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Sex, Age, Specimen part
View SamplesAnalyze the transcriptomes of 347 cells from 10 distinct populations in both of low-coverage (~0.27 million reads per cell) and high-coverage (~5 million reads per cell) to identify cell-type-specific biomarkers, and to compare gene expression across samples specifically for cells of a given type as well as to reconstruct developmental lineages of related cell types.
Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex.
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View SamplesThe SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Age
View SamplesThe three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Significant and systematic expression differentiation in long-lived yeast strains.
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View SamplesEpithelial-mesenchymal transition (EMT) is a pivotal process in development and disease. In carcinogenesis, various signaling pathways are known to trigger EMT by inducing the expression of EMT transcription factors (EMT-TFs) like SNAIL1, ultimately promoting invasion, metastasis and chemoresistance. However, how EMT is executed downstream of EMT-TFs is incompletely understood. Here, using human colorectal cancer (CRC) and mammary cell line models of EMT, we demonstrate that SNAIL1 critically relies on bone morphogenetic protein (BMP) signaling for EMT execution. This activity requires the transcription factor SMAD4 common to BMP/TGFβ pathways, but is TGFβ signaling-independent. Further, we define a signature of BMP-dependent genes in the EMT-transcriptome which orchestrate EMT-induced invasiveness, and are found to be regulated in human CRC transcriptomes and during EMT in vivo. Collectively, our findings substantially augment the knowledge of mechanistic routes whereby EMT can be effectuated, which is relevant for the conceptual understanding and therapeutic targeting of EMT processes.
Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1.
Specimen part
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