Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA886992 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21799623.fastq.gz | Fastqsanger.gz | |||
| SRR21799624.fastq.gz | Fastqsanger.gz | |||
| SRR21799625.fastq.gz | Fastqsanger.gz | |||
| SRR21799626.fastq.gz | Fastqsanger.gz | |||
| SRR21799627.fastq.gz | Fastqsanger.gz |
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Project description:Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides.
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Project description:To explore the mechanism of SCO-derived peptides, we performed RNAseq in cultured neurons added with SCO peptide and control neurons which added with DPBS to identify the expression of some unique genes and possible pathway related to the function of SCO derived peptides. We cofirmed the role of SCO derived peptide which contribute in neuronal development,especially projection developent and cell survival. development and neuronal survival .
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Project description:To explore the role of SCO and its functional mechanism, we performed RNAseq between SCO and hippocampus at different stage to identify the expression of some unique genes and possible pathway related to the function of SCO. We cofirmed the role of SCO in neuronal development and identified three SCO-derived peptides which can contributed to neurite development and neuronal survival .
2024-11-30 | GSE214744 | GEO
Project description:The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. To explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3, and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely thymosin beta 4, thymosin beta 10, and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.
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Project description:Cellular senescence is associated with aging but also impacts various physiological and pathological processes such as embryonic development and wound healing. Factors secreted by senescent cells can affect their microenvironment, including local spreading of senescence. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood however, the presence of hepatic senescence is associated with poor prognosis and extrahepatic organ failure in acute liver disease. Here, using genetic mouse models of hepatocyte-specific senescence, we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence. In patients with acute indeterminate hepatitis, the extent of hepatocellular senescence predicts the occurrence of extrahepatic dysfunction, need for liver transplantation and mortality. We identify the Transforming Growth Factor β (TGFβ) pathway as a critical mediator of systemic spread of senescence and TGFβ inhibition blocks senescence transmission to other organs preventing renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence which, independent of aging, contributes to multi-organ dysfunction.
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Project description:Cellular senescence is associated with aging but also impacts various physiological and pathological processes such as embryonic development and wound healing. Factors secreted by senescent cells can affect their microenvironment, including local spreading of senescence. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood however, the presence of hepatic senescence is associated with poor prognosis and extrahepatic organ failure in acute liver disease. Here, using genetic mouse models of hepatocyte-specific senescence, we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence. In patients with acute indeterminate hepatitis, the extent of hepatocellular senescence predicts the occurrence of extrahepatic dysfunction, need for liver transplantation and mortality. We identify the Transforming Growth Factor Beta (TGFbeta) pathway as a critical mediator of systemic spread of senescence and TGFbeta inhibition blocks senescence transmission to other organs preventing renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence which, independent of aging, contributes to multi-organ dysfunction.
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Project description:Oxidative damage contributes significantly to the pathogenesis of psoriasis. We recently developed antioxidative peptides (UPF peptides) activating the endogenous glutathione system (GSH). In the present study, we analyzed gene expression profiles in the samples of psoriasis patients to find if these peptides could reduce oxidative damage during psoriasis. Peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and from healthy controls were collected and cultivated. Cultured PBMCs were incubated with two different UPF peptides for 12 hours. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST arrays and with quantitative real-time PCR. Gene expression profile in the PBMCs of patients with psoriasis indicated significant up-regulation of the immune response pathway. Treatment with UPF peptides normalized the gene expression pattern in psoriasis samples. Therefore, treatment with antioxidative drugs have potential anti-psoriatic activity. 5 healthy controls (C1-5), 5 psoriasis patients (P1-5), 2 different drugs (upf17 peptide, upf1 peptide) and a control drug. Overall, 30 samples and six groups: PSOR, PSORUPF1, PSORUPF17, CON, CONUPF1, CONUPF17.
2012-08-22 | E-GEOD-40263 | biostudies-arrayexpress
Project description:Oxidative damage contributes significantly to the pathogenesis of psoriasis. We recently developed antioxidative peptides (UPF peptides) activating the endogenous glutathione system (GSH). In the present study, we analyzed gene expression profiles in the samples of psoriasis patients to find if these peptides could reduce oxidative damage during psoriasis. Peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and from healthy controls were collected and cultivated. Cultured PBMCs were incubated with two different UPF peptides for 12 hours. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST arrays and with quantitative real-time PCR. Gene expression profile in the PBMCs of patients with psoriasis indicated significant up-regulation of the immune response pathway. Treatment with UPF peptides normalized the gene expression pattern in psoriasis samples. Therefore, treatment with antioxidative drugs have potential anti-psoriatic activity.
2012-08-22 | GSE40263 | GEO
Project description:The subcommissural organ (SCO) is an ancient and evolutionarily conserved gland in the brain located at the entrance of the aqueduct of Sylvius. It exists in species as distantly related as amphioxus and humans, but the function of the SCO is still mysterious. Comparison of transcriptomes between SCO and non-SCO brain regions revealed three unique genes, namely Sspo, Car3, and Spdef, that are highly enriched in the SCO. We generated the corresponding gene knock-in mouse strains utilizing the Cre/lox recombinase system for specific expression in SCO cells. Genetic ablation of SCO cells at embryonic stages with these strains revealed that SCO excision resulted in severe hydrocephalus and developmental defects in the brain. Abnormalities were also observed for neuronal migration and axon and dendrite development in the cerebral cortex. Taking advantage of non-targeted peptidomic analysis, we identified three SCO-derived peptides, namely thymosin beta 4 (Tβ4), thymosin beta 10 (Tβ10), and NP24. We found that these SCO peptides contributed to neurite development and neuronal survival in vitro. Indeed, application of a cocktail containing Tβ4, Tβ10 and NP24 to SCO-ablated brain ventricles substantially rescued their developmental defects. Our results demonstrate that SCO-derived peptides play critical roles in neuronal development.
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Project description:Peptides represent a major class of cell-cell signaling molecules. Most peptidomic studies have focused on peptides present in brain or other tissues. For a peptide to function in intercellular signaling, it must be secreted. The present study was undertaken to identify the major peptides secreted from mouse brain slices that were cultured in oxygenated buffer for 3-4h. Approximately 75% of the peptides identified in extracts of cultured slices matched the previously reported peptide content of heat-inactivated mouse brain tissue, whereas only 2% matched the peptide content of unheated brain tissue; the latter showed a large number of postmortem changes. As found with extracts of heat-inactivated mouse brain, the extracts of cultured brain slices represented secretory pathway peptides as well as peptides derived from intracellular proteins such as those present in the cytosol and mitochondria. A subset of the peptides detected in the extracts of the cultured slices was detected in the culture media. The vast majority of secreted peptides arose from intracellular proteins and not secretory pathway proteins. The peptide RVD-hemopressin, a CB1 cannabinoid receptor agonist, was detected in culture media, which is consistent with a role for RVD-hemopressin as a non-classical neuropeptide. Taken together with previous studies, the present results show that short-term culture of mouse brain slices is an appropriate system to study peptide secretion, especially the non-conventional pathway(s) by which peptides produced from intracellular proteins are secreted. This article is part of a Special Issue entitled: An Updated Secretome.
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