Single cell RNA sequencing using either an adapted Smart-seq2 protocol on Chx10-GFP (+) retinal progenitor cells; 10x Genomics Chromium Single Cell system across 10 timepoints of mouse retinal development to examine retinal progenitor cell heterogeneity across retinal development and global changes in gene expression from early retinal neuroepithelial cells through specification and differentiation of retinal cell types; 10X Genomics Chromium Single Cell on P14 Nfia/b/x het control or Nfia/b/x tCKO (Chx10-Cre-GFP) retinas Overall design: Examination of transcript expression within 120,840 cells across 10 developmental time-points (14 experiments) via 10x Genomics and 864 cells via an adapted Smart-Seq2 protocol; Characterization of Nfia/b/x mutant phenotypes using single-cell RNA-seq
Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification.
Specimen part, Cell line, Subject
View SamplesPatients with oncogene driven tumors are currently treated with targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors. The inhibited oncogenic pathway often interacts with other signaling pathways and alters predicted therapeutic response. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates pervasive molecular alterations to EGFR, MAPK, and PI3K signaling in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to infer the complex pathway interactions that result from EGFR inhibitor use in cancer cells that contain these these common EGFR network genetic alterations. To do this, we modified the HaCaT keratinocyte cell line model of premalignancy to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background. We then measured gene expression after treating modified HaCaT cells with three EGFR targeted agents (gefitinib, afatinib, and cetuximab) for 24 hours.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Cell line, Treatment
View SamplesTo determine the expression AP2-alpha target genes, global gene expression of 7 HNSCC cell lines with and without cetuximab treatment (100 nM, 24 hrs) and the HaCaT keratinocyte cell line was performed.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Specimen part, Cell line
View SamplesThis study was performed to identify gene expression differences in not otherwise specified soft tissue sarcomas (NOS, malignant fibrous histiocytomas) and correlate them to histological findings and the clinical course. RNA was isolated and differential gene expression was analysed by the microarray technique.
Malignant fibrous histiocytoma--pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study.
Sex
View SamplesWe used microarrays to detail the global program of gene expression during early hESC differentiation to mesendoderm using FBS, with and without RUNX1 depletion.
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
Specimen part, Cell line
View SamplesThe onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that results in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was overrepresented at promoters of genes associated with cancer-related phenotypic traits, such as estrogen response and epithelial-to-mesenchymal transition pathways. Our findings highlight an important role for H3K4ac in predicting epigenetic changes associated with early stages of transformation. In addition, our data provide a valuable resource for understanding epigenetic signatures that correlate with known breast cancer-associated oncogenic pathways. Overall design: RNA-Seq of cell lines MCF10A, MCF7 and MDA-MB-231.
Histone H3 lysine 4 acetylation and methylation dynamics define breast cancer subtypes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Specimen part
View SamplesOsteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcription program essential for bone formation through both genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed. By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation: proliferation, matrix deposition and mineralization, we identified Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) over the course of these stages, we discovered close to 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibited distinct patterns during osteogenesis, and were associated with proximal promoters as well as a large percentage of Runx2 occupancy in non-promoter regions: upstream, introns, exons, transcription termination site (TTS) regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identified novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of extracellular matrix. We demonstrated by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions. Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identifying Nuclear Matrix-Attached DNA Across the Genome.
Specimen part, Cell line
View SamplesWe used microarrays to detail the global programme of gene expression during early hESC differentiation to Mesendoderm using FBS.
Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.
Sex, Cell line, Time
View Samples