Cell Communication and Signaling最新文献

{"title":"Beyond phenotypic markers: rethinking dopaminergic identity in iPSC-derived neurons.","authors":"Duc-Hiep Bach, Thanh Liem Nguyen","doi":"10.1186/s12964-026-03197-0","DOIUrl":"10.1186/s12964-026-03197-0","url":null,"abstract":"<p><p>Human pluripotent stem cell-derived dopaminergic neurons have become central platforms for Parkinson's disease (PD) modeling and regenerative medicine. Current differentiation systems can efficiently generate TH⁺/FOXA2⁺/LMX1A⁺ ventral midbrain-like populations. Although canonical markers remain important components of dopaminergic validation, the field increasingly complements them with single-cell profiling, developmental reference mapping, functional assessment, and transplantation-based evaluation. Nevertheless, marker-positive phenotypic resemblance alone may inadequately capture the full multidimensional identity of substantia nigra pars compacta neurons. Recent single-cell, developmental, and organoid studies indicate that human dopaminergic neurons exist across highly specialized multidimensional states shaped by developmental trajectory, epigenetic regulation, metabolic adaptation, biological aging, and ecosystem-level interactions. On the basis of these observations, we hypothesize that some current in vitro systems may generate neurons with incomplete or context-dependent identity because of accelerated differentiation, strong exogenous patterning, resetting of age-associated features, incomplete metabolic maturation, and the absence of supporting cells and tissue-derived signals. We distinguish these experimentally observed limitations from their conceptual interpretation and propose a testable framework for evaluating dopaminergic identity across developmental, molecular, metabolic, functional, aging-related, and environmental dimensions. This framework identifies improved maturation, representation of biological age, metabolic resilience, and multicellular context as priorities for PD modeling and regenerative neuroscience.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic metabolic adaptation to endurance exercise: temporal and sex differences by multiomics integration and validation.","authors":"Yuan Gao, Zhangyi Tu, Qi Zhao, Jie Peng, Yuan Shu, Junlin Ren, Xueqiang Deng, Yongjun Chen, Yun Zhou, Haimin Zeng, Bofan Chen, Liang Hao","doi":"10.1186/s12964-026-03154-x","DOIUrl":"10.1186/s12964-026-03154-x","url":null,"abstract":"<p><strong>Background: </strong>Although endurance exercise benefits liver health, sex-specific adaptive trajectories remain unclear. This study mapped dynamic liver adaptation in males and females during prolonged training and identified underlying molecular programs.</p><p><strong>Methods: </strong>Using publicly available time-resolved liver multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we established a computational pipeline for differential analysis of transcriptomic, proteomic, phosphoproteomic, and metabolomic data with FDR correction, followed by FGSEA pathway enrichment. Kinase activities were inferred through ortholog mapping and PhosphoSitePlus. Cross-omics co-expression networks were constructed using WGCNA and topological overlap to link omics features with physiological phenotypes. For experimental validation, liver tissues were collected from endurance-trained Sprague-Dawley rats, and key nodes were confirmed by Western blotting, qRT-PCR, and immunofluorescence/immunohistochemical staining. Public scRNA-seq data were further integrated to map multi-omics signals to single-cell resolution and assess functional changes in specific cell types.</p><p><strong>Results: </strong>The hepatic response to exercise stress was stage-specific, shifting from early transcriptional activation to later proteomic and metabolic remodeling. Multi-omics integration revealed distinct sex-associated adaptive trajectories: males were more strongly associated with energy metabolism, redox-related programs, and amino acid/organic acid catabolism, whereas females showed prominent membrane lipid remodeling, proteostasis -related programs, and mitochondrial/ribosomal translational features. Single-cell analysis showed that tissue remodeling occurred without major lineage turnover, instead involving altered communication among pre-existing cell communities. Validation of PPP1R3G identified a protein-dominant exercise-responsive marker, supporting the contribution of post-transcriptional or protein-level regulation.</p><p><strong>Conclusions: </strong>Hepatic adaptation to endurance stress follows a cross-omics evolutionary pattern with sex-specific reprogramming of energy supply and homeostatic maintenance. This time-resolved framework clarifies how exercise improves liver function and supports sex-oriented metabolic interventions and therapeutic target discovery.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBV re-activation is associated with increased mortality and dysregulation of oxidative and polyamine metabolism in pre-acute-on-chronic liver failure.","authors":"Mirco Glitscher, Keerthihan Thiyagarajah, Jianyi Wei, Jannik Sonnenberg, Pia Lembeck, Wenyi Gu, Georgios Grammatikos, Lining Guo, Jonel Trebicka, Guohong Deng, Xianbo Wang, Xin Zheng, Yan Huang, Jinjun Chen, Zhongji Meng, Yanhang Gao, Zhiping Qian, Feng Liu, Xiaobo Lu, Yu Shi, Yubao Zheng, Yingli He, Hai Li, Eberhard Hildt, Kai-Henrik Peiffer","doi":"10.1186/s12964-026-03145-y","DOIUrl":"10.1186/s12964-026-03145-y","url":null,"abstract":"<p><strong>Background/aims: </strong>Acute-on-chronic liver failure (ACLF) is one of the deadliest complications of chronic liver disease yet treatment options are sparse. In Asia, HBV-reactivation (HBVr) is one of the most common triggers. Recently, HBV-associated ACLF was associated with distinct changes in the metabolome. Here, metabolic impacts of HBVr were analysed in-depth in non-ACLF, pre-ACLF and ACLF.</p><p><strong>Methods: </strong>Clinical and metabolic data of 1024 Chinese patients (CATCH-LIFE studies) with chronic HBV mono-infection were analyzed. ACLF was diagnosed according to COSSH criteria. Metabolites in plasma were quantified using LC-MS, compared to non-ACLF and subjected to enrichment and pathway analyses using the database SMPDB via MetaboAnalyst v6.</p><p><strong>Results: </strong>In 1024 patients (611: non-ACLF, 72: pre-ACLF, 341: ACLF), HBVr was present in 20.2% (ACLF) or 33.3% (pre-ACLF) of patients. HBVr increased 28-day mortality in pre-ACLF patients (2.1% in HBVnr vs. 25% in HBVr). Energy metabolism generating reactive oxygen species (ROS) was highly induced in the absence of ROS-detoxifying pathways in pre-ACLF. Urea cycle, thus nitric oxide (NO) build-up, the polyamine metabolism and related pathways were highly increased in both HBVr pre-ACLF and ACLF, shifting pre-ACLF close to mature ACLF. Specific metabolites could be identified as putative markers and key-regulators herein.</p><p><strong>Conclusion: </strong>HBV reactivation induces inflammation, hepatic injury and mortality especially in pre-ACLF patients. Metabolic disruption in the ROS/NO/polyamine axis favors stress and hinders liver regeneration. Findings help identifying and alleviating HBVr-driven progression towards ACLF via pharmacological or biopharmaceutical intervention.</p><p><strong>Trial registration: </strong>Analyses were based on the CATCH-LIFE studies. The CATCH-LIFE studies were registered at Clinical.</p><p><strong>Trials: </strong>gov (Clinical Trial Number: NCT02457637, first registered 2015-01-31 and NCT03641872, first registered 2018-08-14).</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148834958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR2 mediates cell cycle re-entry and survival of neonatal cardiomyocytes in response to injury.","authors":"Julia Nicke, Adrian Goldspink, Malte Menn, Bernd K Fleischmann, Mona Malek Mohammadi","doi":"10.1186/s12964-026-03147-w","DOIUrl":"10.1186/s12964-026-03147-w","url":null,"abstract":"<p><p>Unlike adult hearts, neonatal hearts can regenerate and adapt to stress. To identify both cardioprotective and regenerative mechanisms, we compared activated genes and related signaling pathways in the neonatal mouse heart after myocardial infarction (MI) and after exposure to pressure overload using a neonatal model of transverse aortic constriction (nTAC) at postnatal day 1 (P1). We identified three immune-related genes-Ccl4, S100a8, and C1qa-of high interest, as they encode secreted factors, are highly expressed in the neonatal mouse heart in both injury types, and their receptors are expressed on neonatal cardiomyocytes (nCM) and cardiac endothelial cells (EC). We investigated their effects on primary mouse EC and nCM in vitro. Our study found that the combination of these secreted factors (Pool3) enhances EC and nCM cell cycle re-entry and reduces the rate of apoptosis. Combined in vivo and in vitro transcriptome analyses revealed that Toll-like receptor 2 (TLR2) activation in nCM induces a shared pro-survival and cell cycle re-entry-associated signaling, including upregulation of Bcl2 and Birc5, respectively. The direct and pivotal role of TLR2 in enhancing nCM cell cycle re-entry and survival was further confirmed using TLR2 knockout (KO) nCM, a TLR2 inhibitor, and a TLR2 agonist (zymosan). Moreover, the importance of TLR2 in mediating the adaptive response to pressure overload in neonatal mice was confirmed in TLR2 KO mice, which failed to adapt to pressure overload and exhibited high mortality together with maladaptive cardiac remodeling as early as 7 days post-surgery. Collectively, these findings demonstrate that TLR2 is essential for mediating nCM cell cycle re-entry, survival, and adaptive/regenerative response to injury.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of B cells for osteogenic homeostasis.","authors":"Radost A Saß, Christian H Bucher, Sabine Bartosch, Il-Kang Na, Olaf Penack, Georg N Duda, Katharina Schmidt-Bleek","doi":"10.1186/s12964-026-03128-z","DOIUrl":"10.1186/s12964-026-03128-z","url":null,"abstract":"<p><p>Therapeutic interventions for diseases such as leukemia and autoimmune disorders are increasingly designed to selectively target and deplete specific immune cell subsets over prolonged periods. This can disrupt the homeostasis of the adaptive immune system, with consequences not only for peripheral blood but also for the \"cradle of the immune system\", the bone marrow. This study hypothesized that such immune imbalance due to immune cell depletion therapies impairs the differentiation capacity of mesenchymal stromal cells (MSCs), which are key progenitors of bone cells and are thus essential for maintaining bone health. To validate this hypothesis, a series of cell culture experiments were conducted in which MSCs were stimulated with immune-conditioned media derived from various immune cell subsets. A comprehensive analytical approach was employed to evaluate the differentiating MSCs, including their associated supernatants, deposited collagen, mineralized matrix, and lipid deposition at defined time points during their maturation. Therefore, fluorescence and nonfluorescent histological staining, enzyme-linked immunosorbent assays (ELISAs), and expression analyses with Ribonucleic acid (RNA) were performed. This study demonstrated that, compared with immune-conditioned media from T cells or peripheral blood mononuclear cells (PBMCs), B cell-immune-conditioned media enriched with interleukin 4, bone morphogenetic protein 2 and Dickkopf 1 enhanced the osteogenic differentiation of MSCs in vitro. This positive osteogenic effect is driven primarily by elevated cytokine secretion by stimulated B cells, which in vivo in turn potentially stimulate bone turnover and modulate immune system function. In summary, these data demonstrate an pro-osteogenic and pro-adipogenic influence of B cells on differentiating MSCs in vitro, suggesting that an imbalance in immune cells in the bone marrow perturbs bone homeostasis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual role of PIEZO2 in neuropathic pain: driving peripheral sensitization and enabling mechanical loading-induced analgesia.","authors":"Chongjie Yao, Yuchen Zhang, Dong Xie, Jiayang Yu, Xinyu Zeng, Shizhen Song, Qiuju Chen, Sipeng Huang, Shuaipan Zhang, Qingguang Zhu, Min Fang","doi":"10.1186/s12964-026-03131-4","DOIUrl":"10.1186/s12964-026-03131-4","url":null,"abstract":"<p><strong>Background: </strong>Mechanotherapy, a form of mechanical loading (ML), effectively relieves tactile allodynia-associated neuropathic pain by targeting sensitization points stimulated by PIEZO2, a mechanosensitive ion channel. However, the molecular mechanisms underlying peripheral sensitization and ML-induced analgesia remain unclear. The study aimed to investigate the role of PIEZO2 in neuroinflammatory processes in a rat model of chronic compression injury (CCD) of dorsal root ganglia (DRG).</p><p><strong>Methods: </strong>Mechanical allodynia was assessed via paw withdrawal threshold in male Sprague-Dawley rats. ML was applied at intensities of 2.5-5 N, targeting either sensitization or non-sensitization points, with or without intrathecal administration of the PIEZO2 channel blocker D-GsMTx4. Behavioral assays, patch-clamp electrophysiology, western blot, enzyme-linked immunosorbent assay, RNA sequencing, and non-targeted metabolomics of skin, DRG, and spinal dorsal horn (SDH) were performed to evaluate neuronal excitability, inflammatory markers, and omics-level responses.</p><p><strong>Results: </strong>CCD upregulates PIEZO2 expression in all tissues, indicating mechanical hypersensitivity and neuroinflammation. ML alleviates allodynia while suppressing SDH inflammation and MAPK signaling, especially at 5 N. Functionally blocking PIEZO2 attenuates ML-induced analgesia and downregulates rectifier K⁺ currents in DRG neurons. ML and the inhibition of PIEZO2 function exhibit similar lipid metabolism profiles and downregulate PGE₂ and all-trans-5,6-epoxyretinoic acid.</p><p><strong>Conclusions: </strong>PIEZO2 is essential for peripheral sensitization, as well as ML-induced analgesia, anti-inflammatory, and ion-channel-modulating effects, which may inform the development of novel non-pharmacological strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-stiffness-driven platelet activation emerges as a potential target for breast cancer prevention and treatment.","authors":"Menikae K Heenkenda, Xingyue Wang, Wen Zhong, Annelie Abrahamsson, Nina Reustle, Daniel Aili, Peter Lundberg, Tomas L Lindahl, Charlotta Dabrosin","doi":"10.1186/s12964-026-03138-x","DOIUrl":"10.1186/s12964-026-03138-x","url":null,"abstract":"<p><strong>Background: </strong>High mammographic breast density is a strong independent risk factor for sporadic breast cancer, yet involved mechanisms remain poorly defined. The extracellular compartment plays a critical role in the intercellular communication during tumor initiation and progression. Although several mechanosensitive pathways have been described, the role of platelets (PLTs) in stiffness-driven signaling in the breast is unknown.</p><p><strong>Methods: </strong>Extracellular soluble proteins were sampled in situ from live breast tissue using microdialysis. A total of 108 postmenopausal women were included: women with nondense or dense breasts, women with dense breasts randomized to low-dose acetylsalicylic acid (ASA; 160 mg/day) or no treatment, and patients with estrogen receptor-positive (ER⁺) breast cancer. Breast density was assessed by magnetic resonance imaging. High-dimensional proteomic profiling of 1,158 proteins was performed using proximity extension assays. To investigate stiffness-dependent PLT responses, cells were cultured in a 3D in vitro system with tunable matrix stiffness generated by cross-linked hyaluronic acid, modeling nondense and dense breast tissue.</p><p><strong>Results: </strong>Dense breast tissue exhibited a distinct extracellular proteomic signature enriched for proteins associated with platelet activation, along with alterations in several immunomodulatory pathways. Several PLT-associated proteins were also elevated in ER⁺ breast cancers, supporting their clinical relevance. Post hoc exploratory proteomic analysis of samples from women treated with low-dose ASA did not reveal modulation of these proteins, suggesting that stiffness-induced PLT activation may occur via mechanotransduction rather than biochemical pathways in vivo. Consistently, in the 3D in vitro model, increased matrix stiffness representative of dense breasts promoted a procoagulant PLT phenotype without corresponding changes in classical activation markers.</p><p><strong>Conclusions: </strong>Tissue stiffness is a critical regulator of PLT mechanotransduction in dense breast tissue, contributing to a microenvironment permissive for cancer progression. These findings highlight PLT mechanobiology as a potential target for breast cancer prevention and therapy.</p><p><strong>Clinical trial registration: </strong>EudraCT: 2017-000317-22.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the gap: moonlighting functions of connexins in cancer.","authors":"Carolien Van Damme, Lisa Depestel, Sven Eyckerman, Kaat Durinck","doi":"10.1186/s12964-026-03127-0","DOIUrl":"10.1186/s12964-026-03127-0","url":null,"abstract":"<p><p>Connexins are classically defined as the structural subunits of gap junction channels that mediate direct intercellular communication. In cancer, their role has long been interpreted through this canonical role, with loss of gap junction intercellular communication considered permissive for tumor initiation. Although genomic alterations in connexin genes have been identified across diverse malignancies, their mechanistic implications remain poorly defined, and current cancer treatment strategies largely target channel activity alone. However, accumulating evidence demonstrates that connexins also exert important channel-independent, non-canonical functions that reshape oncogenic signaling networks. These \"moonlighting\" activities, defined as mechanistically distinct functions performed by a single protein, reposition connexins as active regulators of tumor cell behavior rather than passive conduits of small signaling molecules and messengers. Connexin moonlighting functions influence multiple hallmarks of cancer, including proliferation, survival, invasion, and metastatic dissemination, in a context- and stage-dependent manner. These functions help explain the long-standing paradox that connexins can exert both tumor-suppressive and pro-tumorigenic effects. In this Review, we synthesize recent insights into the roles of connexins in cancer, focusing on gap junction-independent functions. We highlight key unresolved mechanistic questions and discuss how an expanded understanding of connexin biology may inform more precise therapeutic strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac function in zebrafish embryos is linked to an androgen receptor-adrenomedullin-proepicardium axis.","authors":"Max Duong Phu, Alessandra Guerrero Samanidis, Sabrina Laibacher, Martina Burczyk, Yara Alkhars, Ana Janovic, Ashraf Al Madhoun, Ilona S Skerjanc, Martin D Burkhalter, Melanie Philipp","doi":"10.1186/s12964-026-03107-4","DOIUrl":"10.1186/s12964-026-03107-4","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart defects (CHDs) comprise the most common congenital malformation affecting nearly 1% of all newborns. In individuals with sex chromosome aneuploidy syndromes, however, the prevalence reaches up to 50% of all livebirths. One commonality to these syndromes is a marked reduction in sex hormones, particularly androgens. Androgen receptor (Ar) insufficiency represents a culprit in the pathophysiology of adult onset cardiovascular disease and arrhythmia, but there are no reports regarding Ar function during heart development. This is surprising as androgens along with its nuclear receptor exist already during early development, even before gonads develop and become functional.</p><p><strong>Methods: </strong>We evaluated the role of the Ar during vertebrate heart development by generating loss-of function in zebrafish embryos via pharmacological inhibition, transient CRISPR/Cas9 treatment, or interference of splicing as well as murine cell culture.</p><p><strong>Results: </strong>Attenuation of Ar function in zebrafish embryos prevents normal cardiac morphology and physiology as apparent by edema, bradycardia and arrhythmia. Molecularly, we identified increased abundance of adrenomedullin (Adm) 2a as a likely cause for the observed defects. Cellularly, these phenomena may be linked to impaired formation of proepicardial cells, which are reported to intermingle with cells of the conduction system and influence cardiac pacing.</p><p><strong>Conclusions: </strong>A disrupted Ar - Adm2 axis possibly contributes to the increased frequency of CHD in individuals suffering from sex chromosome aneuploidy syndrome.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging of hair follicle stem cells and their niche: mechanisms and regenerative therapeutic strategies.","authors":"Siqi Xu, Jiming Guo, Ying Kang, Qinjing Wang, Yue Ming, Weixing Chen, Min Wang, Zhijie Huang, Yisheng Huang, Bo Jia","doi":"10.1186/s12964-026-03086-6","DOIUrl":"10.1186/s12964-026-03086-6","url":null,"abstract":"<p><p>Hair follicles (HFs) are vital skin appendages that perform fundamental functions including protection, thermoregulation, and sensation. Orchestrated by hair follicle stem cells (HFSCs), HFs undergo cyclic regeneration throughout the lifespan. However, during chronological aging, this mini-organ experiences progressive physiological decline, clinically characterized by a marked reduction in hair density and hair graying due to pigmentation dysfunction. This aging process involves HFSC exhaustion accompanied by diminished regenerative potential and differentiation capacity, leading to degenerative changes in the bulge architecture. Concurrently, the niche supporting HFSC homeostasis undergoes multi-dimensional and systemic degradation. This niche deterioration disrupts the delicate balance between HFSC quiescence and activation, further impeding hair regeneration. In this review, we delineate the dynamic anatomical changes throughout the hair growth cycle and describe the alterations of HFSCs during aging. We specifically focus on the mechanisms underlying the multi-dimensional degradation of the HFSC niche at tissue, cellular, and molecular levels. Furthermore, we discuss various therapeutic strategies aimed at ameliorating HF aging, offering potential insights for future clinical translation in hair regeneration. Finally, we propose that integrating spatiotemporal high-resolution technologies with genomic data to further decipher the spatiotemporal behaviors of aging HFSCs and niche cells will facilitate the establishment of a robust mechanistic framework for HFSC and niche aging.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"24 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}