This SuperSeries is composed of the SubSeries listed below.
Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.
Specimen part
View SamplesMyelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and -catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.
Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.
Specimen part
View SamplesZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in EMT-dependent tumor metastasis. While the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is upregulated by activated T cells, specifically in the KLRG1hi effector CD8+ T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8+ T cells following primary and secondary infection with a severe impairment in the generation of the KLRG1hi effector-memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress CD127 and IL-2 in CD8+ T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box-sites in the ZEB2 gene and that T-bet and ZEB2 regulate similar gene-expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Taken together, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8+ T cells.
Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection.
Sex, Age, Specimen part
View SamplesWe sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Overall design: Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples
Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.
Specimen part
View SamplesNuclear receptor Reverb alpha is a component of circadian rythm which could be evolved in cardioprotection strategy. We test if pharmacological modulation of these target could be suitable for cardioprotection after ischemia reperfusion injury
Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.
Specimen part
View SamplesInflammatory bowel diseases (IBD) in humans are characterized by chronic inflammation and gastrointestinal tissue damage, caused by a combination of genetic and environmental factors. It has been largely documented that IBD frequently lead to colorectal cancers (CRC). The identification of causative factors of IBD is thus essential to understand CRC progression and develop therapeutical approaches. Models have been described in which molecular alterations are combined with inflammatory treatments in order to recapitulate IBD-associated CRC. Here, we describe a mouse line, 6fl/fl Villin-Cre, in which inactivation of the gene encoding the integrin alpha-6 subunit (ITGA6) specifically in the intestinal mucosa results into chronic inflammation and intestinal carcinogenesis. In these mice, the loss of integrin alpha-6 beta-4, a receptor mediating the attachment of epithelial cells to laminins, leads to epithelial detachment, hyperplasia, chronic inflammation, rectal prolapses, and ultimately adenocarcinomas. Alterations of differentiation affecting mucus secreting (goblet) cells as well as changes in expression of essential intestinal transcription factors were detected. Thus alpha-6 beta-4 integrin is a key factor for the maintenance of intestinal integrity and its loss may represent a risk factor for tumor progression associated with IBD.
Hemidesmosome integrity protects the colon against colitis and colorectal cancer.
Specimen part
View SamplesTranscriptome analysis of mRNAs extracted from the rectal mucosa of WT and 6IEC-TAM mice, 15 days after tamoxifen treatment
Hemidesmosome integrity protects the colon against colitis and colorectal cancer.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Specimen part, Disease, Disease stage, Subject
View SamplesWe aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI)
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Disease
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