Ask about this productRelated genes to: DLK1 antibody
- Gene:
- DLK1 NIH gene
- Name:
- delta like non-canonical Notch ligand 1
- Previous symbol:
- -
- Synonyms:
- FA1, pG2, Pref-1, ZOG, Delta1
- Chromosome:
- 14q32.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-09
- Date modifiied:
- 2019-04-23
Related products to: DLK1 antibody
Related articles to: DLK1 antibody
- Heart failure with preserved ejection fraction (HFpEF) remains a formidable clinical challenge due to its intricate pathophysiology and the difficulty in early diagnosis. Traditional biomarkers for HFpEF are often insufficient in clinical practice, driving the need for more novel, sensitive diagnostic markers. - Source: PubMed
Publication date: 2026/04/14
Xiaobin LiuYu QinJingjie FengChang LiuShuang ZhangJianing YangJiangping WenYonghong Niu - Paternal environmental exposures program offspring neurodevelopment via sperm epigenetics, yet mechanisms for intergenerational hypothalamic-pituitary-adrenal (HPA) axis dysregulation, a core hub for stress disorders, remain elusive. Using a paternal preconception caffeine exposure (PPCE) rat model with in vitro fertilization to exclude maternal confounders, we uncover a novel pathway linking sperm epigenetics to offspring HPA axis hyperresponsivity. By elevating paternal corticosterone, PPCE induces hypomethylation at the intergenic differentially methylated region (IG-DMR) within sperm Dlk1-Dio3 domain. This epigenetic alteration evades postfertilization reprogramming, persists in offspring hippocampus, and derepresses the maternally expressed miRNA cluster, causing posttranscriptional downregulation of glutaminase (GLS). Hippocampal GLS deficiency impairs glutamatergic neurotransmission in a novel circuit: ventral hippocampal CA1 glutamatergic neurons (vCA1) → piriform cortex γ-aminobutyric acid-ergic neurons (Pir) → paraventricular nucleus corticotropin-releasing hormone neurons (PVN). Chemogenetic activation of this circuit rescues HPA axis hyperresponsivity and affective phenotypes. Clinically, sperm IG-DMR hypomethylation correlates with elevated plasma cortisol in prospective fathers. Importantly, paternal folic acid supplementation prevents these epigenetic alterations and restores offspring stress homeostasis. Our study delineates an intergenerational mechanism and identifies a potentially translatable prenatal intervention strategy. - Source: PubMed
Publication date: 2026/04/30
Lu MengxiDai GaoleZhu SenZhang ShuaiWang TingtingMeng YuanYang FangHan XiaoyiWang HuiKou HaoXu Dan - KIR+NKG2A- natural killer (NK) cells can detect and eliminate malignant and infected cells that have downregulated single HLA class I molecules to escape T cell recognition. So far, these KIRonly NK cells cannot be efficiently expanded in vitro without concomitant co-expression of NKG2A, which modulates their specificity. In this context, we recently demonstrated that circulating innate lymphoid cells 1 (cILC1s) have NK cell progenitor potential and can be differentiated into KIRonly NK cells using murine feeder cells. Here, we established an animal-free culture system enabling the generation and expansion of NK cells from cord blood (CB)-derived cILC1s using human mesenchymal stem cells (MSCs) as feeder cells. Compared to the murine niche provided by the OP9-DL1 cell line, human MSCs generally enabled a much more efficient generation of NK cells, resulting in significantly higher yields of KIR+ NK cells. The frequency of KIRonly NK cells could be further increased by addition of the soluble NOTCH ligand DLL1. Furthermore, we utilized the cILC1/MSC platform to study education of KIRonly NK cells by HLA-C-encoded ligands in a human stem cell niche. This effect was strongest for homozygous (C1/C1) compared to heterozygous (C1/C2) donors, suggesting that cognate KIR/KIR ligand interaction mediates a gene-dosage-dependent education effect. Altogether, this optimized culture protocol overcomes previous limitations by enabling efficient generation of KIR-expressing NK cells in an animal-free, GMP-compatible system. The presented approach may facilitate the clinical translation of NK cell-based strategies for cellular immunotherapy and in addition provides a platform for mechanistic studies of NK cell education. - Source: PubMed
Bennstein Sabrina BReiß JulianWeinhold SandraScherenschlich NadineDegistirici ÖzerRaba KatharinaWalter LutzFischer Johannes CKögler GesineMeisel RolandUhrberg Markus - Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable transmembrane protein with tightly regulated, developmentally restricted expression. It is highly expressed during embryogenesis, where it plays a key role in controlling cellular differentiation and proliferation, but is largely silenced in adult tissues, persisting mainly within stem and progenitor compartments of endocrine organs. Notably, DLK1 is consistently re-expressed across a broad range of malignancies, with the highest prevalence observed in endocrine and neuroendocrine tumours, including adrenocortical carcinoma, phaeochromocytoma/paraganglioma, medullary thyroid carcinoma, and neuroblastoma. DLK1 expression is associated with adverse clinical outcomes and is increasingly implicated in maintaining a de-differentiated, stem-like tumour phenotype that might contribute to tumour progression and therapeutic resistance. The restricted expression of DLK1 in normal adult tissues, combined with its cell-surface localisation and functional relevance in tumour biology, makes it an attractive therapeutic target, particularly in endocrine malignancies where targetable options remain limited. Multiple DLK1-directed strategies are now advancing through preclinical and early clinical development, including afucosylated monoclonal antibodies, antibody-drug conjugates, dendritic cell vaccines, chimeric antigen receptor T-cell therapies, and radioimmunotherapy. Early-phase studies demonstrate encouraging safety profiles and signals of efficacy, with emerging evidence suggesting that tumour-specific factors-such as steroidogenesis, immune microenvironment, and drug efflux mechanisms-may influence response in endocrine cancers. This review collates current evidence on DLK1 biology and therapeutic targeting, with a focus on endocrine and neuroendocrine malignancies. We highlight key novel mechanistic insights, translational challenges, and future opportunities to exploit DLK1 as a precision therapeutic target in these high-need cancer subtypes. - Source: PubMed
Publication date: 2026/04/22
Henry Pittaway James Frederick - To investigate the association between Catenin Beta 1 (CTNNB1) gene polymorphisms and type 2 diabetes mellitus (T2DM), as well as the interacting molecules of CTNNB1. Bioinformatic analysis of publicly available transcriptomic datasets derived from T2DM samples identified a panel of differentially expressed genes (DEGs), among which CTNNB1 exhibited significant differential expression. Subsequent functional enrichment analysis and molecular docking revealed a co-expression network between CTNNB1 and Delta-like 1 homologue (DLK1). A total of 988 subjects including 455 patients with T2DM and 533 healthy controls were included, and the epidemiological and clinical data were collected. Association between SNPs (rs2953, rs4135387, rs1798802) of CTNNB1 and susceptibility to T2DM was analyzed. CTNNB1 expression was quantified in human serum by ELISA. A mouse model of diabetes was induced by a high-fat diet (HFD). The weight, blood glucose levels, and pancreatic morphology were detected. In a diabetes mouse model, CTNNB1 and DLK1 levels were further assessed using ELISA, Western blot, qRT-PCR, and immunohistochemistry. Immunofluorescence staining was also performed on pancreatic tissue sections to evaluate the spatial relationship within islets between β-catenin and DLK1. Integrated analysis of DEGs and pathway enrichment identified CTNNB1 as a key gene in T2DM. Functional enrichment and molecular docking suggested that CTNNB1 and DLK1 may interact through hydrogen bonding. The CTNNB1 gene rs1798802 locus was associated with T2DM. The proportion of T2DM patients was lower in the GG genotype group than in controls (47.7% vs. 52.3%). The GG genotype of the CTNNB1 gene at the rs1798802 tended to protect the individuals from T2DM (OR = 0.640, 95% CI: 0.446-0.918, p = 0.015). Serum levels of CTNNB1 were significantly reduced in patients with T2DM (74.5 pg/mL vs. 23.78 pg/mL). Compared with control mice, HFD-induced T2DM mice showed significantly decreased protein content and gene expression of β-catenin in the pancreatic tissue, while a concurrent decrease was also observed in DLK1 expression. Immunofluorescence staining revealed a significant overlap in the subcellular distribution of CTNNB1 and DLK1, which supported their potential physical interaction within pancreatic islet cells. The CTNNB1 gene exhibits differential expression in T2DM, and its genetic polymorphisms are also associated with the disease. The CTNNB1 gene rs1798802 loci GG genotype may be a protective factor against T2DM. CTNNB1 may interact with DLK1, potentially contributing to the regulation of pancreatic islet function. The Wnt/β-catenin signaling pathway is inhibited in pancreatic islets in T2DM. β-catenin (CTNNB1) is a potential target for the treatment of T2DM. - Source: PubMed
Gan XiaoxueAdeerjiang YilinuerXu MinHe XuanJiang ShengDu Guoli