Germline 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 SamplesCurrent models imply that the FERM domain protein Merlin, encoded by the tumor suppressor NF2, inhibits mitogenic signaling at or near the plasma membrane. Here, we show that the closed, growth inhibitory form of Merlin accumulates in the nucleus, binds to the E3 ubiquitin ligase CRL4DCAF1, and suppresses its activity. Depletion of DCAF1 blocks the promitogenic effect of inactivation of Merlin. Conversely, enforced expression of a Merlin-insensitive mutant of DCAF1 counteracts the antimitogenic effect of Merlin. Re-expression of Merlin and silencing of DCAF1 induce a similar, tumor-suppressive program of gene expression. Tumor-derived mutations invariably disrupt Merlins ability to interact with or inhibit CRL4DCAF1. Finally, depletion of DCAF1 inhibits the hyperproliferation of Schwannoma cells from NF2 patients and suppresses the oncogenic potential of Merlin-deficient tumor cell lines. We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4DCAF1.
Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus.
Specimen part
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.
No sample metadata fields
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesBackground: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored.
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesBackground: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored.
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Specimen part, Disease
View Samples