Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs. Immature DCs were differentiated in vitro from human monocytes under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and the gene expression profile was determined. Hi-DCs expressed novel hypoxia-inducible genes and were characterized by up-regulation of pathways associated with cell movement/migration.
Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.
No sample metadata fields
View SamplesDendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs and maturation into mature DCs. Mature DCs were differentiated in vitro from human monocytes under normoxic or hypoxic conditions and the gene expression profile was determined.
Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.
Specimen part, Disease, Treatment
View SamplesThe rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sex, Specimen part, Treatment, Subject
View SamplesGermline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. Overall design: RNA-sequencing of 12 Smarcb1-deficient mouse cranial nerves and meninges tumors
Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.
Specimen part, Subject
View SamplesGene expression analysis identified a CRC related signature of differentially expressed genes discriminating patients Responder and Non Responder to radiochemotherapy
A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesSummary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or desease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function.
Gene profiling in spinal cord injury shows role of cell cycle in neuronal death.
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View SamplesTo elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD)
Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks.
No sample metadata fields
View SamplesAQM shows acute muscle wasting and weakness. Key aspects of AQM include muscle atrophy and myofilament loss. Gene expression profiling, using muscle biopsies from AQM, neurogenic atrophy and normal controls, showed that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways while only the AQM shows a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways.
Constitutive activation of MAPK cascade in acute quadriplegic myopathy.
No sample metadata fields
View SamplesThe three-dimensional (3D) organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects is still controversial. To determine how changes in chromosome positioning affect transcription we characterized nuclear organization and global gene expression after large-scale chromosomal rearrangements in budding yeast. We used computational modelling and single cell imaging to determine chromosome position and integrated these data with genome-wide transcriptional profiles from RNA sequencing. Chromosome displacement relative to the nuclear periphery has mild but widespread and significant effects on transcription. Our study suggests that basal transcriptional activity is sensitive to radial changes on chromosomal position, and provides support for the functional relevance of budding yeast chromosome-level 3D organization in gene expression. Overall design: We analysed 42 samples in total: wildtype (409) strain (4 replicas), mutant strain 524 (4 replicas), mutant strain 527 (4 replicas), mutant strain 1138 (4 replicas), mutant strain 1228 (4 replicas), mutant strain 1379 (4 replicas), mutant strain 1387 (4 replicas), mutant strain 1380 (4 replicas), mutant strain 1388 (4 replicas), mutant strain 1788 (3 replicas), mutant strain 1793 (3 replicas)
Impact of Chromosome Fusions on 3D Genome Organization and Gene Expression in Budding Yeast.
Specimen part, Cell line, Subject
View SamplesCellular function is strongly dependent on surrounding cells and environmental factors. Current technologies are limited in characterizing the spatial location and unique gene-programs of cells in less structured and dynamic niches. Here we developed a method (NICHE-seq) that combines photoactivatable fluorescent reporters, two-photon microscopy and single-cell RNA-seq to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and unique gene-programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the marginal zone. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways. Overall design: Transcriptional profiling of single cells from the specific immune niches in the lymph node and spleen, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500
Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq.
Specimen part, Cell line, Treatment, Subject
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