Transcriptional profilling of In vitro-primed C.rodentium-specific WT or Caspase-1 deficient Th cells
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PROVIDER: PRJNA591907 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: We reported that caspase-1 is highly expressed in in vitro-primed C.rodentium-specific Th cells. Caspase-1 deficient (Casp1d10) naïve T cells differentiate into pathogen-specific Th17 cells at an suboptimal level and fail to protect against C.rodentium infection. To gain insight into the regulatory pathways exerted by caspase-1 in Th cells, we performed RNA-seq on in vitro-primed WT and Casp1d10 Th cells. Method: We stimulated WT C57/BL6J splenic CD11c+ DCs with 10ug/ml C.rodentium lysate for 5 hours. Then DCs are washed and co-cultured in 1:5 ratio with naïve WT C57/BL6J or Casp1d10 CD4 T cells for 10 days. CFSE-CD90+ (pathogen-specific Th cells) were FACS-sorted and subjected to mRNA-seq analysis. Conclusion: We found that WT Cr-specific Th cells have higher expression of Th17 genes, including Il17a,f,Il22 and Rorc. Casp1Δ10 Cr-specific Th cells exhibited higher expression of iNOS genes and exogenous lipid metabolism genes such as Cd36, suggesting a distinct cellular metabolism potentially regulated by Caspase-1.
2020-01-10 | GSE141062 | GEO
Project description:Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression. Survey of spontateous 24 NB tumors and 5 bone marrow samples in wt and transgenic mice.
2013-05-22 | E-GEOD-42548 | biostudies-arrayexpress
Project description:Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression. Survey of spontateous 13 NB tumors in wt and transgenic mice
2013-05-22 | E-GEOD-42254 | biostudies-arrayexpress
Project description:The project used next generation sequencing for RNA-seq analysis, to identify transcriptome changes associated with tumorigenesis in two different caspase-2 knockout mice models. We describe key changes in both lymphoma and neuroblastoma associated genes in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2-/- tumors, that are strongly associated with neuroblastoma outcome, and which have roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In addition, we found that key changes in gene expression in the EμMyc/Casp2-/- tumors, are associated with increased immune signaling and suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues.
2019-01-28 | GSE124051 | GEO
Project description:Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression.
2013-05-22 | GSE42548 | GEO
Project description:Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression.
2013-05-22 | GSE42254 | GEO
Project description:Transcriptome profiling of caspase-2 deficient lymphomas from EμMyc and neuroblastomas from Th-MycN mice
| PRJNA510620 | ENA
Project description:Profilling normal human placantal proteomes using LTQ-OrbiTrap
2015-05-26 | PXD000754 | Pride
Project description:The Th-inducing POK (Th-POK, also known as cKrox or ZBTB7B) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. We found that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands. Th-POK is not required for mammary gland development in puberty and alveologenesis in pregnancy. Th-POK-deficient mice are defective in secretory activation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. We compared microarray gene expression in mammary glands of lactating wild-type or Th-POK-deficient mice. We show that Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the mammary glands. Thus, Th-POK function as an important regulator of insulin signaling in mammary gland lactation.
2018-02-06 | GSE97566 | GEO
Project description:Profilling normal human placantal proteomes using LTQ-OrbiTrap
2019-06-10 | MSV000083950 | MassIVE