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Items 2425 to 2436 of 13914 total
- Reference(May 2024) Aging Cell 23 8
Centenarian hippocampus displays high levels of astrocytic metallothioneins
AbstractThe hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases. We performed transcriptomic studies in hippocampus samples from individuals of different ages (centenarians [?97 years], old, and young) and identified a differential gene expression pattern in centenarians compared to the other two groups. In particular, several isoforms of metallothioneins (MTs) were highly expressed in centenarians. Moreover, we identified that MTs were mainly expressed in astrocytes. Functional studies in human primary astrocytes revealed that MT1 and MT3 are necessary for their homeostasis maintenance. Overall, these results indicate that the expression of MTs specifically in astrocytes is a mechanism for protection during aging. Higher levels of MT1 and MT3 are detected in hippocampus of very old individuals (over 90) compared with old and young individuals. MTs colocalize with astrocytic markers.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Safety Data SheetCatalog #: Product Name: 60145 Anti-Biotin Antibody, Clone C6D5.1.1 Catalog #: 60145 Product Name: Anti-Biotin Antibody, Clone C6D5.1.1 Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1391Lot #:AllLanguage:EnglishProduct Name:EBV (HLA Class I Control) Peptide PoolCatalog #: 100-1391 Lot #: All Language: English Product Name: EBV (HLA Class I Control) Peptide Pool Reference(Jul 2025) Nature Communications 16Identification of functional non-coding variants associated with orofacial cleft
Oral facial cleft (OFC) comprises cleft lip with or without cleft palate (CL/P) or cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) in many genomic loci where the presumed effector gene (for example, IRF6 in the 1q32 locus) is expressed in embryonic oral epithelium. To identify candidates for functional SNPs at eight such loci we conduct a massively parallel reporter assay in a fetal oral epithelial cell line, revealing SNPs with allele-specific effects on enhancer activity. We filter these SNPs against chromatin-mark evidence of enhancers and test a subset in traditional reporter assays, which support the candidacy of SNPs at loci containing FOXE1, IRF6,  MAFB, TFAP2A, and TP63. For two SNPs near IRF6 and one near FOXE1, we engineer the genome of induced pluripotent stem cells, differentiate the cells into embryonic oral epithelium, and discover allele-specific effects on the levels of effector gene expression, and, in two cases, the binding affinity of transcription factors FOXE1 or ETS2. Conditional analyses of GWAS data suggest the two functional SNPs near IRF6 account for the majority of risk for CL/P at this locus. This study connects genetic variation associated with OFC to mechanisms of pathogenesis. Non-syndromic orofacial cleft is a relatively common congenital anomaly. Many non-coding genetic variants are associated with this disorder but only a subset is functional. Here the authors use reporter assays and stem cells to reveal members of this subset.Catalog #: Product Name: 100-0276 mTeSR™ Plus Catalog #: 100-0276 Product Name: mTeSR™ Plus Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1390Lot #:AllLanguage:EnglishProduct Name:EBV (GP350/GP340) Peptide PoolCatalog #: 100-1390 Lot #: All Language: English Product Name: EBV (GP350/GP340) Peptide Pool Reference(Aug 2024) ACS Omega 9 34LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids
Proteomic analysis of human cerebral organoids may reveal how psychedelics regulate biological processes, shedding light on drug-induced changes in the brain. This study elucidates the proteomic alterations induced by lysergic acid diethylamide (LSD) in human cerebral organoids. By employing high-resolution mass spectrometry-based proteomics, we quantitatively analyzed the differential abundance of proteins in cerebral organoids exposed to LSD. Our findings indicate changes in proteostasis, energy metabolism, and neuroplasticity-related pathways. Specifically, LSD exposure led to alterations in protein synthesis, folding, autophagy, and proteasomal degradation, suggesting a complex interplay in the regulation of neural cell function. Additionally, we observed modulation in glycolysis and oxidative phosphorylation, crucial for cellular energy management and synaptic function. In support of the proteomic data, complementary experiments demonstrated LSD’s potential to enhance neurite outgrowth in vitro, confirming its impact on neuroplasticity. Collectively, our results provide a comprehensive insight into the molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Safety Data SheetProduct Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1389Lot #:AllLanguage:EnglishProduct Name:EBV (LMP2A) Peptide PoolCatalog #: 100-1389 Lot #: All Language: English Product Name: EBV (LMP2A) Peptide Pool Reference(Mar 2024) Frontiers in Molecular Neuroscience 17APOE3 Christchurch modulates ?-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer's cases
A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer’s disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation. ScRNA sequencing revealed regulation of Cadherin and Wnt signaling pathways by APOE3Ch, with immunostaining indicating elevated ?-catenin protein levels. Further in vitro reporter assays unexpectedly demonstrated that ApoE3Ch functions as a Wnt3a signaling enhancer. This work uncovered a neomorphic molecular mechanism of protection of ApoE3 Christchurch, which may serve as the foundation for the future development of protected case-inspired therapeutics targeting AD and tauopathies.Catalog #: Product Name: 05872 ¸é±ð³¢±ð³§¸éâ„¢ 100-0276 mTeSRâ„¢ Plus 08570 STEMdiffâ„¢ Cerebral Organoid Kit Catalog #: 05872 Product Name: ¸é±ð³¢±ð³§¸éâ„¢ Catalog #: 100-0276 Product Name: mTeSRâ„¢ Plus Catalog #: 08570 Product Name: STEMdiffâ„¢ Cerebral Organoid Kit Safety Data SheetCatalog #: Product Name: 60135 Anti-Human CD32 Antibody, Clone FLI8.26 Catalog #: 60135 Product Name: Anti-Human CD32 Antibody, Clone FLI8.26 Product Information SheetCatalog #: Lot #: Language: Product Name: Catalog #:100-1388Lot #:AllLanguage:EnglishProduct Name:EBV (LMP1) Peptide PoolCatalog #: 100-1388 Lot #: All Language: English Product Name: EBV (LMP1) Peptide Pool Reference(May 2025) Nature Communications 16Deciphering signaling mechanisms and developmental dynamics in extraembryonic mesoderm specification from hESCs
Extraembryonic mesoderm (ExM) is crucial for human development, yet its specification is poorly understood. Human embryonic stem cell (hESC)-based models, including embryoids and differentiated derivatives, are emerging as promising tools for studying ExM development. Despite this, the signaling mechanisms and developmental dynamics that underlie ExM specification from hESCs remain challenging to study. Here, we report that the modulation of BMP, WNT, and Nodal signaling pathways can rapidly (4-5 days) and efficiently (?~90%) induce the differentiation of both naive and primed hESCs into ExM-like cells (ExMs). We reveal that ExM specification from hESCs predominantly proceeds through intermediates exhibiting a primitive streak (PS)-like gene expression pattern and delineate the regulatory roles of WNT and Nodal signaling in this process. Furthermore, we find that the initial pluripotent state governs hESC-based ExM specification by influencing signal response, cellular composition, developmental progression, and transcriptional characteristics of the resulting ExMs. Our study provides promising models for dissecting human ExM development and sheds light on the signaling principles, developmental dynamics, and influences of pluripotency states underlying ExM specification from hESCs. Extraembryonic mesoderm (ExM) is crucial but its formation is unclear. Here, authors develop efficient systems to specify ExM from hESCs and dissect the signaling mechanisms, specification dynamics, and impact of pluripotent states in ExM formation.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 05990 °Õ±ð³§¸éâ„¢-·¡8â„¢ Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 05990 Product Name: °Õ±ð³§¸éâ„¢-·¡8â„¢ Items 2425 to 2436 of 13914 total
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