593 FFPE colorectal cancer samples were used to generate three prediction models: Recurrence prediction, 5FU efficacy prediction, and FOLFOX efficacy prediction
Building personalized treatment plans for early-stage colorectal cancer patients.
Specimen part
View SamplesGATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis.
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Specimen part, Cell line
View SamplesTotal RNA was analyzed from either uninduced or -estradiol treated G1E-ER-GATA cells to determine changes in gene expression upon induction of erythroid maturation (treated).
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Specimen part
View SamplesPRDM proteins are tissue specific transcription factors often deregulated in diseases, particularly in cancer where different members have been found to act as oncogenes or tumor suppressors. PRDM5 is a poorly characterized member of the PRDM family for which several studies have reported a high frequency of promoter hypermethylation in cancers of gastrointestinal origin. We report here the characterization of Prdm5 knockout mice in the context of intestinal carcinogenesis. We demonstrate that loss of Prdm5 increases the number of adenomas throughout the murine small intestine on an ApcMin background. By genome-wide ChIP-seq and transcriptome analyses we identify loci encoding proteins involved in metabolic processes as prominent PRDM5 targets and characterize monoacylglycerol lipase (Mgll) as a direct PRDM5 target in human colon cancer cells and in Prdm5 mutant mouse intestines. Moreover, we report the downregulation of PRDM5 protein expression in human colon neoplastic lesions. In summary, our data provide the first causal link between Prdm5 loss and intestinal carcinogenesis and uncover an extensive and novel PRDM5 target repertoire likely facilitating the tumor suppressive functions of PRDM5.
Prdm5 suppresses Apc(Min)-driven intestinal adenomas and regulates monoacylglycerol lipase expression.
No sample metadata fields
View SamplesWe performed microarray analysis to examine the differential gene expression profiles between Prdm1 (Blimp-1)-deleted and control keratinocytes. Keratinocytes isolated from Prdm1-floxed K5-CreER positive (CKO) mice were cultured in the presence of 4OHT to induce deletion of the Prdm1 allele in vitro. Prdm1-floxed K5-CreER positive (CKO) keratinocytes treated with the ethanol solvent control (EtOH) or Prdm1-floxed K5-CreER negative (control) keratinocytes treated with 4OHT or EtOH served as controls. Microarray analyses revealed that there were 93 genes up-regulated and 109 genes down-regulated by more than 2-fold in the CKO + 4OHT group in comparison with the CKO + EtOH, Ctrl + 4OHT or Ctrl + EtOH groups. Several corneocytes-related genes, including Rptn, Lce1f, Krt1 and Lce1d, are significantly down-regulated and several cytokines/chemokines, including Cxcl1, Cxcl2, Cxcl5 and Il24, are significantly up-regulated upon the deletion of Prdm1 in vitro.
Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice.
Specimen part, Treatment
View SamplesWe present an organoid regeneration assay in which freshly dissociated human mammary epithelial cells from healthy donors are grown in adherent/rigid or floating/compliant collagen I gels. In both conditions, luminal progenitors (CD49f+EpCAM+) form spheres, whereas basal cells (CD49fhiEpCAM-) generate branched ductal structures. However, in compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland.
Quantification of regenerative potential in primary human mammary epithelial cells.
Sex, Specimen part, Disease, Subject
View SamplesConstitutive activation of the anti-apoptotic NF-B signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) that is characterized by adverse survival. Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-B pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 mutants in the NF-B negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of -Catenin and its destruction complex consisting of APC, AXIN1, CK1 and GSK3 to oncogenic CARMA1. Recruitment of the -Catenin destruction complex was independent of CARMA1-BCL10-MALT1 (CBM) complex formation or constitutive NF-B activation and promoted the stabilization of -Catenin. Elevated -Catenin expression was detected in cell lines and biopsies from ABC DLBCL that rely on chronic BCR signaling. Increased -Catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF dependent transcriptional activation in response to WNT signaling. In conjunction with NF-B, -Catenin enhanced expression of immune suppressive IL-10 and repressed anti-tumoral CCL3, indicating that -Catenin may induce a favorable tumor microenvironment. Thus, parallel activation of NF-B and -Catenin signaling by gain-of-function mutations in CARMA1 can augment WNT stimulation and is required for maintaining high expression of distinct NF-B target genes and can thereby trigger cell intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.
Oncogenic CARMA1 couples NF-κB and β-catenin signaling in diffuse large B-cell lymphomas.
Specimen part, Cell line
View SamplesAbstract
Breast cancer-associated fibroblasts confer AKT1-mediated epigenetic silencing of Cystatin M in epithelial cells.
No sample metadata fields
View SamplesBackground: Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition. Methodology/Principal findings: Our aim was to analyze the dynamics of differentiation of two closely related stromal cell types, adipose tissue-derived MSCs and dermal fibroblasts (FBs) along adipogenic, osteogenic and chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated donor-matched MSCs and FBs are distinct populations that stay different upon differentiation into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression occur early in differentiation and persist over time in both MSCs and FBs. Further, MSCs and FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation. Conclusion: Our findings suggest that stromal stem cells including adipose-derived MSCs and dermal FBs exploit different molecular mechanisms of differentiation to reach a common cell fate. The early mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation between MSCs and FBs. Overall design: A total of 91 samples were analyzed by multiplex RNA-seq. Samples represented replicates from two patients, two cell types and three differentiation protocols, as indicated by the sample annotation. 5 barcodes were unused, but the corresponding FASTQ files are included for completeness.
RNA-seq analysis reveals different dynamics of differentiation of human dermis- and adipose-derived stromal stem cells.
Specimen part, Treatment, Subject
View SamplesAlthough the basic anatomical sub-divisions of the larval mosquito gut were established several decades ago, information regarding their exact physiological roles is rather scarce. Several studies have reported differences between larval gut compartments in various morphological and physiological aspects. Unfortunately, the fragmentary and incomplete nature of this information makes it hard to establish clear links to the specific and/or unique physiological roles of each gut region.
A microarray-based analysis of transcriptional compartmentalization in the alimentary canal of Anopheles gambiae (Diptera: Culicidae) larvae.
No sample metadata fields
View Samples