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GSE20570
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Methylation of histone H3 lysine 4 (H3K4me) at actively expressed, cell type-specific genes is established during development by the Trithorax group of epigenetic regulators. In mammals, the Trithorax family includes KMT2A-D (MLL1-4), a family of SET domain proteins that function in large complexes to impart mono-, di-, and trimethylation at H3K4. Individual KMT2s and their co-factors are essential for embryonic development and the establishment of correct gene expression patterns, presumably by demarcating the active and accessible regions of the genome in a cell specific and heritable manner. Despite the importance of H3K4me marks in development, little is known about the importance of histone methylation in maintaining gene expression patterns in fully differentiated and non-dividing cell types. In this report, we utilized an inducible cardiac-specific Cre driver to delete the PTIP protein, a key component of a H3K4me complex, and ask whether this activity is still required to maintain the phenotype of terminally differentiated cardiomyocytes. Our results demonstrate that reducing the H3K4me3 marks is sufficient to alter gene expression patterns and significantly augment systolic heart function. These results clearly show that maintenance of H3K4me3 marks is necessary for the stability of the transcriptional program in differentiated cells. The array we performed allowed us to identify genes that are regulated by PTIP and histone methylation.
Publication Title
Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFß1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties (EP) of the cardiomyocytes compared to co-culture with dermal fibroblasts (DFs). The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration. Overall design: We performed RNA-seq for hPSC-CFs, primary CFs and DFs to compare the gene expression for each type of fibroblasts. We also added the hPSC-CMs and hPSCs as the positive and negativ controls in the RNA-seq to compare the gene expression for cardaic factors. Five cell types (hPSC-CFs, human adult CFs and DFs, hPSC-CMs and hPSCs) with 2 biological replicates for each cell type of a total 10 samples were sequenced.
Publication Title
Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Publication Title
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization. Overall design: mRNA profiles of T-cells obtained from hu-Mice infected with wild-type or Tax-PBM HTLV-1 were generated by deep-sequencing in triplicates using Illumina's Hiseq3000 platform.
Publication Title
PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- IlluminaHiSeq2500
Description
Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of ~400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts are more sensitive to a change in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, single-cell gene expression and chromatin accessibility analysis shows that loci with consistent NL contacts are expressed at lower levels and are more consistently inaccessible than loci with lower contact frequencies. These results highlight fundamental principles of single cell chromatin organization. Overall design: In this dataset, single-cell mRNA sequencing results from 96 single KBM7 cells have been deposited
Publication Title
Genome-wide maps of nuclear lamina interactions in single human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Stabilin-1/CLEVER-1 is a multidomain protein present in lymphatic and vascular endothelial cells and in M2 immunosuppressive macrophages. Stabilin-1 functions in scavenging, endocytosis and leukocyte adhesion to and transmigration through the endothelial cells. We have analyzed the putative functions of Stabilin-1 in blood monocytes and found that in healthy individuals 60-80% of both CD14+CD16- and CD14+C16+ monocytes, but not CD14dimCD16+ monocytes, expressed Stabilin-1 on the surface. Microarray and RNAseq analysis was performed to get more insight into the effect of Stabilin-1 expression on human monocytes transcriptome. Overall design: The transcriptome of human monocytes transfected with Stabilin-1 siRNA was compared to that of control siRNA transfected monocytes
Publication Title
Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Vascular adhesion protein-1 (VAP-1) is an endothelial cell-surface protein. It is also an enzyme posessing semicarbazide-sensitive amine oxidase activity (EC.1.4.3.6). VAP-1 is involved in leukocyte traffic. To study the role of VAP-1 in tumor immunity, we compared gene expression profiles in melanomas growing in VAP-1 -/- mice and their wid-type littermates.
Publication Title
Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Stabilin-1/CLEVER-1 is a multidomain protein present in lymphatic and vascular endothelial cells and in M2 immunosuppressive macrophages. Stabilin-1 functions in scavenging, endocytosis and leukocyte adhesion to and transmigration through the endothelial cells. Overall design: The transcriptome of liver tissue in 2wk old and E17.5 Stab1 knock-out mice was compared to that of corresponding wild type mice
Publication Title
Enhanced Antibody Production in Clever-1/Stabilin-1-Deficient Mice.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The neuronal ceroid lipofuscinoses (NCL) are a group of childhood inherited neurodegenerative disorders characterized by blindness, early dementia and pronounced cortical atrophy. The similar pathological and clinical profiles of different forms of NCL suggest that common disease mechanisms may be involved. Here, we have performed quantitative gene expression profiling of cortex from targeted knock out mice produced for Cln1 and Cln5 to explore NCL-associated molecular pathways. Combined microarray datasets from both mouse models exposed a common affected pathway: genes regulating cytoskeletal dynamics and neuronal growth cone stabilization display similar aberrations. We analyzed locus specific gene expression and showed regional clustering of Cln1 and three major genes of this pathway, further supporting a close functional relationship between the corresponding gene products, Cap1, Ptprf and Ptp4a2. The evidence from the gene expression data was substantiated by immunohistochemical staining data of Cln1-/- and Cln5-/- cortical neurons. These primary neurons displayed abnormalities in beta-tubulin and actin as well as abnormal intracellular distribution of growth cone associated proteins GAP-43, synapsin and Rab3. Our data provide the first evidence for a common molecular pathogenesis behind neuronal degeneration in CLN1 and CLN5. Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCL.
Publication Title
Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells.
Publication Title
Plasticity of blood- and lymphatic endothelial cells and marker identification.
Sample Metadata Fields
Cell line
View Samples