Ulcerative 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
View SamplesWe studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. This study provides human genome-wide mapping and expression analyses for EVI1 that will be useful for the research community.
Functional features of EVI1 and EVI1Δ324 isoforms of MECOM gene in genome-wide transcription regulation and oncogenicity.
Cell line
View SamplesEmerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231) by reprogramming cancer cells to a stem-like state. We discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.
HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.
Specimen part, Cell line
View SamplesThe transcription factor Meis1 is preferentially expressed in hematopoietic stem cells (HSCs) and over-expressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. Using inducible knock-out mice, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over long term while steady-state hematopoiesis was sustained in the absence of Meis1. Bone marrow cells of Meis1 deficient mice showed reduced colony formation, contained significantly fewer numbers of long- term HSCs and these Meis1-deficient HSCs exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species (ROS) in HSCs and decreased expression of genes implicated in hypoxia response. Finally, ROS scavenging by N-acetyl cysteine or stabilization of hypoxia-signaling by knockdown of the VHL protein led to reversal of the effects of Meis1-deletion. Taken together, these results demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism.
Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress.
No sample metadata fields
View SamplesIn order to define the genes responsible for the growth and survival of a human castration-resistant prostate cancer cell line, a short term (doxycycline inducible) knockdown system was developed and utilized. Three independent 22Rv1 cell isolates were derived for each of the following doxycycline-inducible shRNAs (shGFP, shAR3, and shVav3) (AR3 = AR-V7). The cells were grown in androgen depleted conditions, plus or minus doxycycline, for three days. RNA from the 18 samples was then sent to the University of Miami Genetics Core for RNA Integrity Number (RIN) evaluation and microarray analysis. Genes differentially regulated by AR-V7 knock-down or VAV3 knock-down were explored as downstream targets of AR-V7 or VAV3, respectively.
Identification of an oncogenic network with prognostic and therapeutic value in prostate cancer.
Specimen part, Cell line
View SamplesNeural stem cells (NSCs) are considered to be the cell-of-origin of brain tumor stem cells. To identify the genetic pathways responsible for the transformation of normal NSCs to brain-tumor-initiating cells, we used Sleeping Beauty (SB) transposons, to mutagenize NSCs. Mobilized SB transposons induced the immortalization of NSCs. Immortalized NSCs induced tumors upon subcutaneous transplantation in immunocompromized mice. To further classify the immortalized cells and mouse tumors, we performed Gene Set Enrichment Analysis (GSEA) using DNA microarray data.
Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells.
Specimen part
View SamplesBcl11b plays an important role in postnatal dentate gyrus development and adult neurogenesis. To determine its role in adult neurogenesis independant from postnatal development the Bcl11b mutation was induced at the age of 2 months.
Stability and Function of Hippocampal Mossy Fiber Synapses Depend on <i>Bcl11b/Ctip2</i>.
Specimen part
View SamplesDuring neocortical development, neurons undergo polarization, oriented migration, and layer type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons. Bcl11a-deficient late-born neurons fail to correctly switch from multipolar to bipolar morphology resulting in impaired radial migration. We show that the expression of Sema3c is increased in migrating Bcl11a-deficient neurons and that Bcl11a is a direct negative regulator of Sema3c transcription. In vivo gain-of-function and rescue experiments demonstrate that Sema3c is a major downstream effector of Bcl11a required for the cell polarity switch and for the migration of upper layer neurons. Our data uncover a novel Bcl11a/Sema3c-dependent regulatory pathway used by migrating cortical neurons.
Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c.
Specimen part
View SamplesHuman CD4+ T cells and CD14+ monocytes from healthy donors were co-cultured with anti-CD3 for three days in the presence or absence of TNF-alpha mAb (Adalimumab). Classical Th17 cells (Th17) or those generated in the presence of the inhibitor (iTh17) were then sorted and analyzed by full transcriptome microarray analysis.
TNF-α blockade induces IL-10 expression in human CD4+ T cells.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors.
Specimen part, Cell line
View Samples