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SRP148277
Homo sapiens
30 Downloadable Samples
Illumina HiSeq 2500
Description
The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. Here, we investigated the properties of endothelial cells (ECs), isolated from four human major organsthe heart, lung, liver, and kidneys in individual fetal tissues at three months'' gestation, at gene expression, and at cellular function levels. We showed that organ-specific ECs have distinct expression patterns of gene clusters, which support their specific organ development and functions. These ECs displayed distinct barrier properties, angiogenic potential, and metabolic rate and support specific organ functions. Our findings showed the link between human EC heterogeneity and organ development and can be exploited therapeutically to contribute in organ regeneration, disease modeling, as well as guiding differentiation of tissue-specific ECs from human pluripotent stem cells. Overall design: We examined the human fetal organ sets from three donors, constituting three biological replicates at 3 months'' gestation (100-125 days). At this stage, all four major organs of interest - the heart, kidney, lung, and liver - have an established microvascular supply and exhibit organ-specific function. The heart beats at 120-160 bpm and is approximately 2 cm, the lungs have developed the entire air-conducting bronchial tree up to 20 generations with respiratory ducts and start to form barriers between alveoli and blood vessels, the liver is the major site of blood cell production and has also started to produce bile, and the kidneys have established nephrons and start to produce urine.
Publication Title
Human Organ-Specific Endothelial Cell Heterogeneity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Kidney peritubular capillaries are particularly susceptible to rarefaction and regeneration-limited after exposure to toxins or injuries. Studying these kidney microvessels remain challenging, primarily resulting from difficulties imaging in vivo, as well as isolating and culturing kidney microvascular cells in vitro, in particular in a three-dimensional (3D) microenvironment with proper hemodynamics. Here, we developed methods to isolate, purify, and characterize human kidney peritubular microvascular endothelial cells (hKMECs), and reconstituted a 3D kidney microvasculature in collagen matrix. Compared to other endothelial cells, isolated hKMECs are very sensitive to VEGF for survival and growth, and have a high vasculogenic but low angiogenic potential. Under flow, they formed a fenestrated endothelium with a comprehensive permeability barrier. When exposed to calcineurin inhibitors, hKMECs formed microvessels displayed cell retraction, broken fenestrae, and swollen endothelium, which led to a thrombogenic luminal wall and erythrocytes extravasations into the subendothelial space. Our study recapitulated the human kidney microvascular structure and function, and shed lights on potential mechanistic studies of kidney specific injuries and diseases.
Publication Title
A Novel Three-Dimensional Human Peritubular Microvascular System.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP1 (iron regulatory protein 1).
Publication Title
Identification of target mRNAs of regulatory RNA-binding proteins using mRNP immunopurification and microarrays.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Study of HP1 Knock Down on gene expression and splicing regulation in Human HeLa cells
Publication Title
Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transcriptome analysis of depletion of DYRK1A in HeLa cells
Publication Title
DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1-mediated transcriptional repression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The present research is devoted to the identification of gene(s) severely affected by EMD mutations, leading to striated muscle laminopathies and more specifically the cardiomyopathy. For this purpose, we developped a large-scale gene expression approach on heart and skeletal tissues from Emd KO mouse model.
Publication Title
Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 29 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The mitochondrial respiratory chain is composed of lipoprotein complexes imbedded in the inner mitochondrial membrane. This chain of enzymes transfers electrons from NADH and FADH2, provided from divers metabolic pathways, to oxygen. It couples the transfer of electrons to the translocation of protons across the membrane. Several clinical syndromes have been associated with respiratory dysfunction caused by mitochondrial or nuclear mutations. A number of mutations in the mitochondrial genes encoding for cytochrome b (CYTB) and cytochrome oxidase (COX 1, 2 and 3) have been linked with diseases. We are using yeast mutants to characterize the deleterious effect of mutations reported in patients on the assembly and catalytic properties of the affected enzymes, and to study the impact of mutations in nuclear genes, such as OXA1, encoding for factors required for the assembly of the respiratory complexes. In this work, we monitored the effects of the mutations causing respiratory defect on the whole genome expression. We compared the change in gene expression in rho0 cells (with a complete deletion of the mitochondrial genome, and by consequence without respiratory chain), in cells with either a single defective enzyme or several, and in cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin. The impact of the mutations on the respiratory function ranged from mild to severe. The expression of approx. 350 genes was changed in at least one mutant. Cluster analysis was performed using the Cluster program (Eisen, 1998, PNAS 95:14863). Four groups of genes were studied in more details: Group A, the most repressed genes; Group B, the most over-expressed genes; Group C, genes more repressed in rho0 and Doxa1 cells; and Group D, genes more over-expressed in Doxa1.
Publication Title
Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.
Sample Metadata Fields
Compound
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Overall design: Four dendritic cell subpopulations from mouse mesenteric lymphnodes were sorted and compared in their gene expression profile
Publication Title
Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Overall design: Sorted naïve CD45.1 OT-II CD4 T cells were co-cultured with four dendritic cell subpopulations sorted from mouse mesenteric lymphnodes. 24h later OT-II cells were sorted again and compared in their gene expression profile.
Publication Title
Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Populus trichocarpa
- 18 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We studied the changes that occur in gene transcription during seasonal senescence in Populus trichocarpa pioneer leaves and fine roots. Plant senescence is a strictly regulated physiological process that allows relocating of valuable nutrients from senescent tissues before death. It might be induced by internal or external factors and among them, phytohormones play an undoubtedly significant role. Senescence was extensively studied in leaves, but the aging of other ephemeral organs, located underground, and its drivers are still poorly understood. We focused on collective results to fill in the knowledge gap about senescence of fine, absorptive roots and leaves in order to check if there are universal mechanisms involved during plant organ senescence. Transcriptional profiling was conducted with the use of microarrays to identify genes involved in developmental PCD. Samples were collected three times during a growth season. The first collection was considered as a control and was collected in early summer (July 7–15) when leaves and the root system were fully developed and functional. The second group of leaf and root samples were harvested in early autumn (October 1–7) when chlorophyll levels in leaves had decreased by approximately 40% and when fine roots had changed in color from white to brown. The third group of samples were harvested in the middle of autumn (November 2–9) when chlorophyll levels in leaves decreased by approximately 65% and fine roots were dark brown or black color. Our results reveal the important role of phytohormones in regulating the senescence of both studied organs. The transcriptomic analyses showed significant changes in gene expression that are associated with phytohormones, especially with ABA and jasmonates. We conclude that phytohormonal regulation of senescence in roots and leaves is organ-specific. In roots, phytohormones are involved indirectly in regulation of senescence by increasing tolerance for cold or resistance for pathogens, whereas such correlation was not observed in leaves.
Publication Title
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (<i>Populus trichocarpa</i>).
Sample Metadata Fields
Specimen part
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