TBX18 antibody - C-terminal region (ARP37832_P050)
- Known as:
- TBX18 (anti-) - C-terminal region (ARP37832_P050)
- Catalog number:
- arp37832_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- TBX18 antibody - C-terminal region (ARP37832_P050)
Related genes to: TBX18 antibody - C-terminal region (ARP37832_P050)
- Gene:
- TBX18 NIH gene
- Name:
- T-box 18
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 6q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2016-10-05
Related products to: TBX18 antibody - C-terminal region (ARP37832_P050)
Related articles to: TBX18 antibody - C-terminal region (ARP37832_P050)
- Gene therapy-based biological pacemakers have been proposed as an alternative to their hardware-based counterparts. In this context, short-term ectopic expression of the T-box transcription factor 18 (TBX18) in the ventricle has been reported to generate potent short-term pacemaker function in various animal models. Here, we investigated the impact of adeno-associated virus (AAV)-mediated long-term expression of TBX18, and compared the outcomes to those of the pacemaker ion channel Hcn2. Our findings revealed that CMV-driven ectopic TBX18 expression in mouse hearts led to severe cardiac fibrosis. At lower, non-fibrogenic levels, TBX18 maintained its transcriptional function but failed to induce pacemaker phenotypes. TBX18-expressing cells showed suppressed expression of key working myocardial genes, but the pacemaker gene program was not induced. Electrophysiological studies showed abnormal automaticity in TBX18-expressing cells, combined with prolonged repolarization and various current changes. However, no hyperpolarization-activated funny current was detected. In a complete AV-block rat model, AAV-mediated Hcn2 expression induced robust ectopic pacemaker activity in the presence of isoproterenol, whereas TBX18 expression neither generated such activity nor augmented Hcn2-mediated pacing. In conclusion, at functionally non-fibrogenic levels, TBX18 is neither sufficient nor necessary to induce pacemaker activity. In contrast, Hcn2 generates reliable pacing, making it a more viable candidate for biological pacemaker development. - Source: PubMed
Publication date: 2026/06/11
Wang JiananRivaud Mathilde RKlerk MischaBoender Arie RVisser Ruud NSparrius RinskeLee Hee Youngvan Duijvenboden KarelZhou HuilingYang YutingKramer Emiel JmPark Kyung HoPark Larry CSchrödel SilkeThirion ChristianEhrke-Schulz EricEhrhardt AnjaKirzner Osne FNeef KlausTan Hanno LVerkerk Arie OChristoffels Vincent MBoink Gerard Jj - Epicardial mesothelium plays a pivotal role in postinfarction cardiac repair by generating fibroblasts, producing extracellular matrix, and releasing paracrine mechanisms. However, interspecies differences have not been sufficiently studied, particularly in in vivo models of scar-free healing such as the African spiny mouse (). This study aimed to compare the profibrotic response of epicardial mesothelial cells (MCs) from and C57BL/6 mice to hypoxic stress, a key factor in postinfarction recovery. We isolated epicardial MCs from the African spiny mouse (), a species with documented cardiac regenerative capabilities, and from C57BL/6 laboratory mice. Using a CoCl-induced hypoxia model in vitro, we assessed cell viability, morphological changes, and expression of epithelial and fibroblast markers. In vivo, following experimental myocardial infarction (MI), we evaluated tissue hypoxia (pimonidazole adducts), epicardial activation (layer thickness, Wt1 and TBX18 progenitor cells), and collagen accumulation. The study was conducted using real-time PCR, Western blotting, immunohistochemical analysis and microscopic examination. In vitro, MCs from both species exhibited an epithelial-like phenotype under normoxic conditions, expressing E-cadherin and cytokeratin 18. Hypoxia (200 µM CoCl) induced a comparable response in both and C57BL/6 cells, characterized by a shift to a spindle-shaped, fibroblast-like morphology, decreased E-cadherin expression, and increased pro-collagen 1 and α-SMA expression. Following MI, both species exhibited similarly extensive hypoxic areas affecting the epicardial zone. Epicardial activation dynamics were comparable: from day 3 post-MI, epicardial thickness increased significantly, and Wt1 and TBX18 progenitor cells accumulated, peaking during the first week. Collagen accumulation in the epicardial region was similar between species, although the number of Wt1 cells was higher in C57BL/6 on day 7. Despite the well-known superior regenerative capacity of spiny mice, epicardial MCs from and C57BL/6 demonstrated similar signs of profibrotic responses to hypoxic stimulation both in vitro and following MI. These findings suggest that species-specific regenerative outcomes may not be attributable to differential acute epicardial sensitivity to hypoxia, but rather to downstream mechanisms or additional factors influencing the cardiac repair process. This study provides the first characterization of epicardial MCs and establishes a foundation for further investigation of evolutionarily conserved and species-specific mechanisms of cardiac regeneration. - Source: PubMed
Publication date: 2026/05/13
Dergilev KonstantinDolgodvorova AleriaTsokolaeva ZoyaIarushkina IrinaBeloglazova IrinaGoltseva YuliaParfyonova Yelena - Regulatory networks that maintain cardiomyocyte identity are not completely understood. Here, we have examined the relationship of the transcription factors Nr2f1a and Isl1, which, respectively, repress and promote pacemaker cardiomyocyte (PC) differentiation within the venous pole of zebrafish atria. Using zebrafish nr2f1a;isl1 mutants, we found that loss of Isl1 exacerbates the inability to maintain the atrial cardiomyocyte (AC) identity found in nr2f1a mutant hearts. Subsequently, while nr2f1a;isl1 mutants have a failure of PC differentiation and their ACs are unable to transdifferentiate into PC identity, ACs in nr2f1a;isl1 mutant hearts lose myocardial marker expression, gain epicardial cell (EC) gene expression and exit the myocardial layer. Single-cell RNA-sequencing analysis of hearts supports the observation that the ACs and ECs of nr2f1a;isl1 mutant embryos share common myocardial and EC transcriptomic signatures. Depletion of tcf21 and tbx18 in nr2f1a;isl1 mutants was sufficient to prevent the acquisition of EC identity within putatively transdifferentiating ACs. Thus, our results reveal reiterative requirements for Nr2f and Isl1 transcription factors in binary fate decisions within the genetic hierarchy that maintains distinct AC, PC and EC identities at the venous pole of vertebrate hearts. - Source: PubMed
Publication date: 2026/06/03
Martin Kendall EFernandes Andrew TSayed MohammedHanlon Margaret AFallon SamuelLim Hee-WoongWaxman Joshua S - Early pregnancy loss (EPL), particularly when recurrent, represents a profoundly distressing experience for affected couples. Although chromosomal abnormalities are the most common cause of EPL, a substantial proportion of cases, especially those involving euploid embryos, remain unexplained. In this study, we investigated the potential contribution of rare monogenic variants to euploid EPL using whole-exome sequencing (WES). WES was performed on 66 euploid products of conceptions (POCs) from EPLs occurring before 12 gestational weeks. A molecular diagnosis with a high level of confidence, defined as the presence of pathogenic or likely pathogenic (P/LP) variant(s) consistent with the expected mode of inheritance, was established in 13/66 POCs (19.7%). These included one large 21q22.12-q22.3 duplication encompassing and . P/LP small variants were detected in , , , , , , , , and , representing genes with variable degrees of prior association with developmental phenotypes and, in some cases, limited or no evidence for embryonic lethality. In an additional 9/66 POCs (13.6%), findings were suggestive but not conclusive for a monogenic contribution. These included four cases with compound heterozygosity involving a pathogenic variant and a variant of uncertain significance (VUS) in autosomal recessive genes (, , , and ), as well as five cases harboring single heterozygous VUS in autosomal dominant genes (, , , , and ). The pathogenic relevance of these variants remains uncertain, particularly in the absence of functional validation. The implicated genes were clustered in biological categories: 1) genes plausibly associated with prenatal or early embryonic lethality, 2) genes causing severe congenital disorders not typically considered embryonically lethal, and 3) genes linked to later-onset or susceptibility phenotypes. These observations are consistent with a spectrum model in which highly deleterious variants may act as primary drivers of embryonic demise, whereas variants with reduced penetrance, later-onset associations or uncertain significance may contribute in a multifactorial context, potentially interacting with additional genetic, maternal or environmental factors. In conclusion, our findings suggest that monogenic variants may contribute to a subset of euploid EPL cases, although the strength of evidence varies considerably across detected variants. The integration of WES into the evaluation of recurrent euploid pregnancy loss holds promise but should be interpreted with caution. Further studies incorporating functional analyses, larger cohorts, and parental data are needed to clarify causality and to define the clinical utility of such approaches in genetic counseling, recurrence-risk assessment, and reproductive planning. - Source: PubMed
Publication date: 2026/05/14
Bozhinovski GjNoveski PTerzikj MKubelka-Sabit KPlaseska-Karanfilska D - Mutations in BMP4 have been associated with malformations of the urinary tract in human patients. Genetic studies in mice have shown that these defects are linked to the expression of Bmp4 in the mesenchymal primordium of the ureter, where it acts as a critical signal for coordinated cytodifferentiation of the mesenchymal and epithelial tissues. Here, we used unbiased transcriptional profiling of ureters with genetic depletion of Bmp4 and pharmacological inhibition of BMP4 signaling to decipher the gene regulatory network controlled by BMP4 in the early ureter, focusing on transcription factors as possible drivers of cytodifferentiation. We show that in Bmp4-deficient ureters, expression of Grhl3, Msx2, Pparg, Trp63, and Foxa1 in the epithelial compartment and of Gata6, Hopx, Id2, Id4, Myocd, Snai1, and Tbx18 in the mesenchymal primordium is reduced. Expression of Msx2, Pparg, Gata6, Id genes, Tbx18, and Snai1 requires direct BMP4 signaling input, whereas reduced expression of the other genes is likely due to secondary changes, including increased retinoic acid signaling. Conditional gene targeting of Smad4 revealed that BMP4-dependent activation of transcription factor genes is mediated in part by SMAD effectors in both ureteral tissues. Thus, our work links BMP4 (signaling) to known transcriptional regulators of ureteral cytodifferentiation and uncovers additional factors that may be relevant to this program. - Source: PubMed
Deuper LenaHense NicolasBeckers AnjaThiesler HaukeMamo Tamrat MBergmann FlorianHildebrandt HerbertTrowe Mark-OliverKispert Andreas