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
- Intracytoplasmic sperm injection (ICSI) is widely used to treat human infertility, yet its effects on offspring fertility remain unclear. As infertile gametes are used in human ICSI procedures, it has remained unclear whether the procedure per se influences fertility of the resulting offspring. Here, we report on increased abortion rates and the induction of immunotolerance breakdown in mice following ICSI. Although sperm concentration was normal, sperm from ICSI-derived males showed higher curvilinear velocity and greater amplitude of lateral head displacement, suggesting a potentially increased fertilization capacity. However, when ICSI-produced males were naturally mated with wild-type females, 27.1% of the fetuses were aborted, compared to a loss of 7.5% of fetuses in control pregnancies, despite identical H2 haplotypes. Analysis of the placenta revealed infiltrating macrophages and granulocytes, as well as increased levels of 8-oxoguanine. This was accompanied by activation of innate immunity and significant downregulation of microRNAs located in the Dlk1-Dio3 microRNA cluster. Several organs of the grand-offspring exhibited inflammation. Therefore, ICSI procedure using wild-type gametes impairs the fertility of ICSI-derived male offspring by activating innate immunity during pregnancy. - Source: PubMed
Publication date: 2026/05/07
Kanatsu-Shinohara MitoShiromoto YusukeOgonuki NarumiInoue KimikoMochida KeijiKabashima KenjiKong YingyiToyokuni ShinyaYamamoto TakuyaOgura AtsuoShinohara Takashi - 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