Transcriptome analysis of transplanted vascular organoid grafts under cranial window at the time of thrombosis after SARS-CoV-2 spike-ECD infusion
Ontology highlight
ABSTRACT: We evaluated virus-induced damages in perfused human blood vessels from iPS-derived vascular organoid (iVO). By taking advantage of the cranial window model, iVOs were transplanted to develop human blood vessels by anastomosing the recipient mouse circulatory system. we infused SARS-CoV-2 spike protein (extracellular domain, ECD) in the mouse to determine the impact on chimeric human-mouse blood vessels formed under the cranial window. Our iVO transplantation studies indicated that Spike protein could specifically target human endothelial cells, but not murine endothelial cells, which leads to neutrophil migration by creating a coagulopathic milieu and therein generating microthrombi.
Project description:Transcriptome analysis of transplanted vascular organoid grafts under cranial window at the time of thrombosis after SARS-CoV-2 spike-ECD infusion
Project description:Purpose: To study the expression and function of a novel cell cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer (PC) pathogenesis. Experimental Design: Immunohistochemical expression profiling of Ecd was done in non-neoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in PC progression, Ecd was stably knocked down in PC cell line followed by in vitro and in vivo functional assays. Results: Normal pancreatic ducts show very weak to no Ecd expression compared to significant positive expression in PC tissues (mean±SE composite score: 0.3±0.2 and 3.8±0.2 respectively, p<0.0001) as well as in PanIN precursor lesions with a progressive increase in Ecd expression with increasing dysplasia (PanIN-1 to PanIN-3). Analysis of matched primary tumors and metastases from PC patients revealed that Ecd is highly expressed in both primary pancreatic tumor and in distant metastatic sites. Further, knockdown of Ecd suppressed cell proliferation in vitro and tumorigenicity of PC cells in mice orthotopic tumors. Microarray study revealed that Ecd regulates expression of glucose transporter GLUT4 in PC cells and was subsequently shown to modulate glucose uptake, lactate production and ATP generation by PC cells. Finally, knockdown of Ecd also reduced level of pAkt, key signaling molecule known to regulate aerobic glycolysis in cancer cells. Conclusion: Ecd is a novel tumor promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells. Two-condition experiment, Ecd knockdown vs Scrambled cells. Biological replicates: 3 Ecd knockdownl, 3 Scrambled, independently grown and harvested. One replicate per array
Project description:Purpose: To study the expression and function of a novel cell cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer (PC) pathogenesis. Experimental Design: Immunohistochemical expression profiling of Ecd was done in non-neoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in PC progression, Ecd was stably knocked down in PC cell line followed by in vitro and in vivo functional assays. Results: Normal pancreatic ducts show very weak to no Ecd expression compared to significant positive expression in PC tissues (mean±SE composite score: 0.3±0.2 and 3.8±0.2 respectively, p<0.0001) as well as in PanIN precursor lesions with a progressive increase in Ecd expression with increasing dysplasia (PanIN-1 to PanIN-3). Analysis of matched primary tumors and metastases from PC patients revealed that Ecd is highly expressed in both primary pancreatic tumor and in distant metastatic sites. Further, knockdown of Ecd suppressed cell proliferation in vitro and tumorigenicity of PC cells in mice orthotopic tumors. Microarray study revealed that Ecd regulates expression of glucose transporter GLUT4 in PC cells and was subsequently shown to modulate glucose uptake, lactate production and ATP generation by PC cells. Finally, knockdown of Ecd also reduced level of pAkt, key signaling molecule known to regulate aerobic glycolysis in cancer cells. Conclusion: Ecd is a novel tumor promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells.
Project description:Overexpression of ECD in mammary gland promotes mammary tumorigenesis. To determine the plausible mechanism of how ECD contributes the oncogenesis, we performed RNAseq analysis of three independent control mice mammary glands (6 months old) and four independent ECD transgenic mammary tumors. Out of these four tumors, T1a and T1b were adenosquamous carcinoma type, T3 was Spindle cell carcinoma type and T4 was papillary carcinoma. RNA was isolated from the respective samples and RNAseq was performed.
Project description:C2C12 cells expressing constitutively active hN1âECD were activated by complete DAPT washout for 1h or 6h, or left in 10 uM DAPT 2 Samples and 1 Control
Project description:Identification of the interaction partners of the protein ecdysoneless (Ecd) in Drosophila melanogaster S2 cells as well as profiling of the changes in binding for mutant, truncated Ecd del34 protein.
Project description:This is a single arm, phase 2, open-label, multicenter trial in patients with metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and documented mutation of extra cellular domain EGFR (ECD-EGFR).
Project description:Exam change in the whole-cell and nuclear proteome circadian proteome in response to environmental circadian disruption (ECD) in mouse liver