Ask about this productRelated genes to: NOTCH1 antibody
- Gene:
- NOTCH1 NIH gene
- Name:
- notch receptor 1
- Previous symbol:
- TAN1
- Synonyms:
- -
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-02-13
- Date modifiied:
- 2019-04-23
Related products to: NOTCH1 antibody
Related articles to: NOTCH1 antibody
- The Notch1 signaling pathway, via the Notch1 receptor and its endogenous ligands, has been suggested to play a role in heart development, as mutations in Notch1 and associated genes are associated with abnormal development of the myocardium, aortic valve, and outflow tract. The cell lineages receiving this signaling are, however, still unclear, partly owing to technical difficulties in labeling Notch1 signaling rather than Notch1 receptor expression. To identify the cell lineages that receive Notch1 signal during heart development, we re-analyzed publicly available single-cell RNA-sequencing data from human embryos (post-conception weeks 6, 8, 12, and 19) and mouse embryos (embryonic days 12.5, 14.5, and 16.5). We found that endothelial cells expressed Notch1 in both species. To confirm Notch1 signaling rather than Notch1 receptor expression in heart development, we carried out transgenic mouse experiments that enabled tracing of both past and ongoing Notch1 signaling by combining the Notch1 receptor protein with the Gal4/UAS and Cre/loxP systems. Past Notch1 signal analysis confirmed that coronary endothelial cells, in addition to a small proportion of endocardial cells, received Notch1 signals during development, consistent with our findings in single-cell RNA-seq re-analysis. Ongoing Notch1 signaling was observed in the surface-covering cells of the vascular lumens, although its colocalization with an endothelial marker (Pecam1/Cd31) was unclear. Collectively, our findings suggested that coronary endothelial cells are Notch1 signal receivers, which should contribute to understanding the pathogenesis of congenital heart diseases. - Source: PubMed
Publication date: 2026/08/07
Watabe YoshitokuTakahashi SatoruYoshihara Masaharu - Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies. - Source: PubMed
Publication date: 2026/08/14
Zhou QiangKong FeiLi DechengRan ZhaoshouXu Jilin - To investigate the clinical value of dynamic monitoring of plasma circulating tumor DNA (ctDNA) in evaluating the efficacy of immunotherapy for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected at baseline and after every 2-3 treatment cycles from 94 patients with advanced ESCC receiving second-line sintilimab monotherapy in the ORIENT-2 study. Targeted sequencing was performed to analyze somatic variants in ctDNA, and the molecular tumor burden index (mTBI) was calculated to assess dynamic changes in ctDNA. Imaging examinations were conducted synchronously with plasma sample collection, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). A total of 614 somatic mutations were detected in 93 eligible baseline plasma samples, with a median of 6 mutations per sample. Missense mutations were the most frequent mutation type. The baseline mutational profile revealed frequently mutated genes including TP53 (82%), CDKN2B (23%), and NOTCH1 (22%). In the 68 patients with both baseline and post-2-cycle plasma samples, no significant changes were observed in the variant allele frequencies (VAFs) of core driver genes before and after treatment (all ＞0.05), and no newly emerged core driver gene mutations were identified. CCND1 copy number variation was associated with shorter progression-free survival (PFS) (=1.88, 95% : 1.08-3.27), while mutations in other genes, including TP53 and NOTCH1, showed no association with PFS (all ＞0.05). None of the frequently mutated genes were associated with overall survival (OS) (all ＞0.05). Among the 68 patients, 11 (15.9%) achieved ctDNA clearance, none of whom showed tumor progression on concurrent imaging evaluation. The remaining 57 patients had ctDNA that became positive or remained persistently positive, of whom 30 (52.6%) showed tumor progression on imaging, with a statistically significant difference between groups (=0.002). Compared with patients whose ctDNA became or remained positive, those with ctDNA clearance exhibited significantly delayed tumor progression (=2.05, 95% : 1.06-3.96), but ctDNA status after 2 cycles did not significantly affect OS (=1.38, 95% : 0.62-3.09). After 2 cycles of treatment, patients in the low mTBI group had a higher disease control rate (DCR) than those in the high mTBI group [73.5% (25/34) vs. 38.2% (13/34), =0.007], as well as superior PFS (=2.80, 95% : 1.65-4.75) and OS (=3.54, 95% : 1.95-6.42). Dynamic changes in mTBI were highly consistent with concurrent imaging response assessments. The molecular response group had a significantly higher DCR than the non-response group [87.5% (21/24) vs. 42.2% (19/45), ＜0.001], as well as superior PFS (=2.39, 95% : 1.41-4.06) and OS (=2.77, 95% : 1.46-5.22). Among 32 patients with stable disease (SD) at the first imaging evaluation after 2 cycles, those in the molecular response group had comparable PFS with the non-response group (=1.03, 95% : 0.51-2.08, =0.942), but significantly longer OS (=3.12, 95% : 1.20-8.06). Dynamic monitoring of the ctDNA-based molecular tumor burden index (mTBI) provides real-time and sensitive molecular information for evaluating the efficacy of immunotherapy in advanced ESCC, demonstrating definite clinical value for personalized treatment management. - Source: PubMed
Wang B YWang H KLi JYe S SXu J M - Myocardial infarction (MI) necessitates the promotion of angiogenesis to improve prognosis. saponins (PQS), bioactive constituents of a medicinal and edible homologous plant, are known for their cardiovascular benefits, but their epigenetic mechanisms in post-MI angiogenesis remain unclear. In this study, PQS was obtained through a water extraction method followed by stepwise enrichment via ethanol elution. Surgical ligation of the left anterior descending (LAD) coronary artery was performed to establish an MI model in male C57BL/6 mice. The therapeutic effects on MI in each group were assessed through histopathological staining and echocardiography. The therapeutic effects of PQS on hypoxic human umbilical vein endothelial cells (HUVECs) were evaluated using tube formation assays, scratch assays, CD31 immunofluorescence, and Western blot (WB). Network pharmacology analysis, Bisulfite Sequencing PCR (BSP) detection, PCR, and WB were utilized to examine the influence of DNMT3b on Notch1 methylation. Cellular Thermal Shift Assay (CETSA) and Co-Immunoprecipitation (Co-IP) assays were employed to ascertain the binding interaction and stability between PQS and DNMT3b. Here, we demonstrate that PQS directly binds DNMT3b, thereby reversing aberrant DNA methylation at the Notch1 promoter and activating the Notch1/ubiquitin-specific protease 5 (USP5)/signal transducer and activator of transcription 3 (STAT3) signaling axis, thereby enhancing endothelial cell migration, tube formation, and angiogenesis in MI models. Ginsenoside Rc, ginsenoside Rh4, and vinaginsenoside R1 were identified as the key active components with the strongest DNMT3b binding affinity and angiogenic activity, with ginsenoside Rc demonstrating the most significant therapeutic effects. These findings reveal a novel epigenetic mechanism and confirm that PQS, particularly ginsenoside Rc, is a highly promising bioactive compound for promoting angiogenesis following MI. - Source: PubMed
Publication date: 2026/08/14
Yao Jun-HanBi YuBu Gang-TaoDong Han-YaYang NanKuang Hai-XueLi Meng-MengLiu Yan - Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML) and contributes to leukemogenesis, treatment response, and clinical heterogeneity. While genome-wide methylation studies have identified prognostic methylation signatures, the impact of DNA methylation within pharmacologic pathways and AML-relevant disease genes remains incompletely understood. We investigated the association of DNA methylation in genes of pharmacokinetic/pharmacodynamic (PK/PD) pathways of drugs used to treat AML and in myeloid leukemia-related genes with treatment outcomes in pediatric AML. - Source: PubMed
Publication date: 2026/07/31
Alshameri NaifahMarchi FranciscoCao XueyuanRubnitz Jeffrey ERibeiro Raul CMeshinchi SoheilPounds Stanley BLamba Jatinder K