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- Safety Data Sheet
Catalog #: Product Name: 74142 Hydrocortisone 74144 Hydrocortisone Catalog #: 74142 Product Name: Hydrocortisone Catalog #: 74144 Product Name: Hydrocortisone - Safety Data Sheet
Catalog #: Product Name: 79040 Total RNA Purification Kit Catalog #: 79040 Product Name: Total RNA Purification Kit - Product Information Sheet
Catalog #: Lot #: Language: Product Name: Catalog #:100-1407Lot #:AllLanguage:EnglishProduct Name:Candida (MP65) Peptide PoolCatalog #: 100-1407 Lot #: All Language: English Product Name: Candida (MP65) Peptide Pool - Reference(Dec 2024) Journal of Inflammation Research 17
Esophageal Cancer-Related Gene-4 Contributes to Lipopolysaccharide-Induced Ion Channel Dysfunction in hiPSC-Derived Cardiomyocytes
Background and PurposeEsophageal cancer-related gene-4 (ECRG4) participate in inflammation process and can interact with the innate immunity complex TLR4-MD2-CD14 on human granulocytes. In addition, ECRG4 participate in modulation of ion channel function and electrical activity of cardiomyocytes. However, the exact mechanism is unknown. This study aimed to test our hypothesis that ECRG4 contributes to inflammation-induced ion channel dysfunctions in cardiomyocytes.MethodsHuman-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from three donors were treated with lipopolysaccharide (LPS) to establish an endotoxin-induced inflammatory model. Immunostaining, real-time PCR, and patch-clamp techniques were used for the study.ResultsECRG4 was detected in hiPSC-CMs at different differentiation time. LPS treatment increased ECRG4 expression in hiPSC-CMs. Knockdown of ECRG4 decreased the expression level of Toll-Like-Receptor 4 (TLR4, a LPS receptor) and its associated genes and inflammatory cytokines. Furthermore, ECRG4 knockdown shortened the action potential duration (APD) and intercepted LPS-induced APD prolongation by enhancing ISK (small conductance calcium-activated K channel current) and attenuating INCX (Na/Ca exchanger current). Overexpression of ECRG4 mimicked LPS effects on ISK and INCX, which could be prevented by NF?B signaling blockers.ConclusionThis study demonstrated that LPS effects on cardiac ion channel function were mediated by the upregulation of ECRG4, which affects NF?B signaling. Our findings support the roles of ECRG4 in inflammatory responses and the ion channel dysfunctions induced by LPS challenge.Catalog #: Product Name: 05990 °Õ±ð³§¸éâ„¢-·¡8â„¢ Catalog #: 05990 Product Name: °Õ±ð³§¸éâ„¢-·¡8â„¢ Safety Data SheetCatalog #: Product Name: 79040 Total RNA Purification Kit Catalog #: 79040 Product Name: Total RNA Purification Kit Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1406Lot #:AllLanguage:EnglishProduct Name:HHV1 (gD) Peptide PoolCatalog #: 100-1406 Lot #: All Language: English Product Name: HHV1 (gD) Peptide Pool Reference(Oct 2024) eBioMedicine 109 1Homology-independent targeted insertion-mediated derivation of M1-biased macrophages harbouring Megf10 and CD3? from human pluripotent stem cells
SummaryBackgroundMacrophages engineered with chimeric antigen receptors (CAR) are suitable for immunotherapy based on their immunomodulatory activity and ability to infiltrate solid tumours. However, the production and application of genetically edited, highly effective, and mass-produced CAR-modified macrophages (CAR-Ms) are challenging.MethodsHere, we used homology-independent targeted insertion (HITI) for site-directed CAR integration into the safe-harbour region of human pluripotent stem cells (hPSCs). This approach, together with a simple differentiation protocol, produced stable and highly effective CAR-Ms without heterogeneity.FindingsThese engineered cells phagocytosed cancer cells, leading to significant inhibition of cancer-cell proliferation in vitro and in vivo. Furthermore, the engineered CARs, which incorporated a combination of CD3? and Megf10 (referred to as FRP5M?), markedly enhanced the antitumour effect of CAR-Ms by promoting M1, but not M2, polarisation. FRP5M? promoted M1 polarisation via nuclear factor kappa B (NF-?B), ERK, and STAT1 signalling, and concurrently inhibited STAT3 signalling even under M2 conditions. These features of CAR-Ms modulated the tumour microenvironment by activating inflammatory signalling, inducing M1 polarisation of bystander non-CAR macrophages, and enhancing the infiltration of T cells in cancer spheroids.InterpretationOur findings suggest that CAR-Ms have promise as immunotherapeutics. In conclusion, the guided insertion of CAR containing CD3? and Megf10 domains is an effective strategy for the immunotherapy of solid tumours.FundingThis work was supported by KRIBB Research Initiative Program Grant (KGM4562431, KGM5282423) and a Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korean government (Ministry of Science and ICT,10.13039/501100003625Ministry of Health and Welfare) (22A0304L1-01).Catalog #: Product Name: 05872 ¸é±ð³¢±ð³§¸éâ„¢ 85850 ³¾°Õ±ð³§¸éâ„¢1 05230 STEMdiffâ„¢ Trilineage Differentiation Kit Catalog #: 05872 Product Name: ¸é±ð³¢±ð³§¸éâ„¢ Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 05230 Product Name: STEMdiffâ„¢ Trilineage Differentiation Kit Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1405Lot #:AllLanguage:EnglishProduct Name:CMV (UL44) Peptide PoolCatalog #: 100-1405 Lot #: All Language: English Product Name: CMV (UL44) Peptide Pool Reference(May 2024) Molecular Systems Biology 20 7Uncovering the dynamics and consequences of RNA isoform changes during neuronal differentiation
Static gene expression programs have been extensively characterized in stem cells and mature human cells. However, the dynamics of RNA isoform changes upon cell-state-transitions during cell differentiation, the determinants and functional consequences have largely remained unclear. Here, we established an improved model for human neurogenesis in vitro that is amenable for systems-wide analyses of gene expression. Our multi-omics analysis reveals that the pronounced alterations in cell morphology correlate strongly with widespread changes in RNA isoform expression. Our approach identifies thousands of new RNA isoforms that are expressed at distinct differentiation stages. RNA isoforms mainly arise from exon skipping and the alternative usage of transcription start and polyadenylation sites during human neurogenesis. The transcript isoform changes can remodel the identity and functions of protein isoforms. Finally, our study identifies a set of RNA binding proteins as a potential determinant of differentiation stage-specific global isoform changes. This work supports the view of regulated isoform changes that underlie state-transitions during neurogenesis. Synopsis Multi-omics analysis of a newly established human neuronal cell differentiation model reveals widespread dynamic changes in RNA isoform expression, their functional consequences and potential determinants, providing evidence that they underlie cell-state-transitions during neurogenesis. Dynamic changes in RNA and protein levels are strongly correlated during all stages of neuronal differentiation.Nanopore sequencing (ONT-seq) during human neurogenesis reveals 12,019 non-annotated RNA isoforms, a large number of which are differentially expressed during differentiation.70% of new RNA isoforms result from the use of alternative transcription start sites (TSSs) or polyadenylation (pA) sites and exon skipping.RNA isoform changes underlie protein isoform changes during human neurogenesis as revealed by integrating ONT-seq, RNA-seq and proteomics time course data.RNA motif enrichment, RNA-seq and available CLIP-seq data uncover a set of RNA binding proteins (RBPs) as potential determinants of differentiation stage-specific global isoform changes. Multi-omics analysis of a newly established human neuronal cell differentiation model reveals widespread dynamic changes in RNA isoform expression, their functional consequences and potential determinants, providing evidence that they underlie cell-state-transitions during neurogenesis.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Safety Data SheetCatalog #: Product Name: 07900 DNase I Solution (1 mg/mL) Catalog #: 07900 Product Name: DNase I Solution (1 mg/mL) Safety Data SheetCatalog #: Product Name: 79020 Genomic DNA Purification Kit Catalog #: 79020 Product Name: Genomic DNA Purification Kit Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1404Lot #:AllLanguage:EnglishProduct Name:HHV8 (K8.1) Peptide PoolCatalog #: 100-1404 Lot #: All Language: English Product Name: HHV8 (K8.1) Peptide Pool Items 2377 to 2388 of 13914 total
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