This SuperSeries is composed of the SubSeries listed below.
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Specimen part
View SamplesTranscriptional programmes involved in the eukaryotic cell cycle are activated sequentially throughout the process. In particular, the set of genes required for S and G2-M phases are highly conserved and induced one after the other.
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
Cell line
View SamplesStromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely non-coding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent anti-viral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine anti-viral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of anti-viral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate cross-talk with BrCa cells by utilizing exosomes to instigate anti-viral signaling. This expands BrCa subpopulations adept at resisting therapy and re-initiating tumor growth.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
No sample metadata fields
View SamplesStromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely non-coding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent anti-viral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine anti-viral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of anti-viral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate cross-talk with BrCa cells by utilizing exosomes to instigate anti-viral signaling. This expands BrCa subpopulations adept at resisting therapy and re-initiating tumor growth.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.
Specimen part
View SamplesA global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res. 2012 Dec;40(22):11339-51.
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.
Specimen part
View SamplesGrowth factors (GFs) suppression by steroid hormones recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids. Overall design: RNA-Seq – EGF treatemnt for 60 min of WT and DNMT1a and DNMT3b double-knockout HCT116 cells
Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone.
Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.
Sex, Age, Specimen part
View SamplesWe investigated DNA methylomes of 227 pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles.
Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.
Sex, Age, Specimen part
View Samples