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CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment. 基于CRISPR/Cas的表观基因组编辑用于成骨谱系承诺。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-06-05 DOI: 10.1007/s00441-026-04076-3
Tengbo Pei, Weina Yang, Yutian Lei, Zihan Qu, Yufang Gao, Minjie Zhang, Tao Xu, Qifu Wen, Qiang Liu
{"title":"CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment.","authors":"Tengbo Pei, Weina Yang, Yutian Lei, Zihan Qu, Yufang Gao, Minjie Zhang, Tao Xu, Qifu Wen, Qiang Liu","doi":"10.1007/s00441-026-04076-3","DOIUrl":"10.1007/s00441-026-04076-3","url":null,"abstract":"<p><p>Bone regeneration remains constrained by incomplete osteogenic commitment of mesenchymal stem cells (MSCs), underscoring the need for precise lineage control. CRISPR/Cas-based epigenome editing provides programmable access to chromatin regulators without altering the DNA sequence, and catalytically inactive Cas9 (dCas9) fused to transcriptional activators, repressors, or chromatin modifiers enables locus-specific modulation of key osteogenic networks, including RUNX2, OSX, and BMP2, while suppressing inhibitory loci such as PPARG, SOST, and DKK1. Multiplex strategies further allow the concurrent activation of osteogenic genes and repression of adipogenic or Wnt antagonists, reshaping lineage allocation in vitro and in vivo. Delivery innovations-from AAV vectors and lipid nanoparticles to biomaterial scaffolds and extracellular vesicles-support local and systemic applications with increasing precision, while whole-genome chromatin profiling and high-fidelity Cas variants reduce off-target risk, and CRISPRoff/on platforms provide reversible and heritable control of transcriptional states. Proof-of-concept studies in small animals demonstrate bone repair in preclinical models, with emerging large-animal data highlighting translational potential. Remaining challenges include payload size, immunogenicity, durability of epigenetic states, GMP-grade manufacturing, and regulatory classification. Looking ahead, advances such as AI-guided gRNA libraries, mechano-responsive scaffolds, and long-term tracking of epigenetic memory may yield durable \"smart\" osteo-epigenetic therapies. Collectively, CRISPR/dCas9-based epigenome editing is progressing from mechanistic exploration toward clinically viable strategies for skeletal regeneration.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FGF19 promotes cartilage destruction in the progress of temporomandibular joint osteoarthritis. FGF19在颞下颌关节骨性关节炎的发展过程中促进软骨破坏。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-06-05 DOI: 10.1007/s00441-026-04080-7
Haoran Chen, Yujia Cui, Yi Liu, Caixia Pi, Jianing Wu, Jianxun Sun, Xian Liu, Tao Zuo, Jing Xie
{"title":"FGF19 promotes cartilage destruction in the progress of temporomandibular joint osteoarthritis.","authors":"Haoran Chen, Yujia Cui, Yi Liu, Caixia Pi, Jianing Wu, Jianxun Sun, Xian Liu, Tao Zuo, Jing Xie","doi":"10.1007/s00441-026-04080-7","DOIUrl":"10.1007/s00441-026-04080-7","url":null,"abstract":"<p><p>Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease characterized by the progressive deterioration of the condylar cartilage, compensatory remodeling of subchondral bone, and persistent synovial inflammation. The onset of TMJOA is accompanied by the activation of cytokines, which exacerbate the imbalance in joint homeostasis and accelerate the destruction and even irreversible degradation of joint structures. FGF19, as an important multifunctional fibroblast growth factor, has been reported to be substantially up-regulated in the cavity of osteoarthritis joint. However, its role in TMJOA progression remains unclear. In this study, we investigated its role in the condyle cartilage in TMJOA. We first established a mouse TMJOA model by unilateral anterior crossbite (UAC) and achieved overexpression of FGF19 by direct injection of adeno-associated virus carrying the Fgf19 gene. We found that FGF19 exacerbated the progressive deterioration of cartilage-subchondral bone unit in the progression of TMJOA. FGF19 accelerated the phenotypic transformation from mature cartilage to hypertrophic cartilage by reducing the expression of collagen type II (COL2A1) and aggrecan, enhancing the expression of collagen type X (COL10A1), matrix metallopeptidase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), and exhibiting a fibrocartilage-associated change in the cartilage layer by increasing the expression of collagen type I alpha 1 and 2 (COL1A1 and COL1A2). Furthermore, FGF19 induces calcification progression of cartilage hypertrophic layer by up-regulating the expression of dentin matrix acidic phosphoprotein 1 (DMP1) via transcription factor osterix (OSX). These data provide evidence of the importance of FGF19 in the progression of TMJOA and show potential cues for interventions of cartilage disease.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anatomy of the hypothalamic-pituitary axis and buccal lobe in the holocephalan Callorhinchus callorynchus. 红颈全头海马下丘脑-垂体轴及颊叶解剖。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-06-03 DOI: 10.1007/s00441-026-04078-1
Camila Harillo, Cynthia A Awruch, Marcelo Santo, Gabriela C López, María R Pérez, Fabricio A Vigliano, Vance L Trudeau, Gustavo M Somoza
{"title":"Anatomy of the hypothalamic-pituitary axis and buccal lobe in the holocephalan Callorhinchus callorynchus.","authors":"Camila Harillo, Cynthia A Awruch, Marcelo Santo, Gabriela C López, María R Pérez, Fabricio A Vigliano, Vance L Trudeau, Gustavo M Somoza","doi":"10.1007/s00441-026-04078-1","DOIUrl":"10.1007/s00441-026-04078-1","url":null,"abstract":"<p><p>Chimeras (Holocephali) occupy a pivotal phylogenetic position, being the oldest jawed vertebrate, for understanding the evolution of hypothalamic-pituitary organization in vertebrates. However, the structural organization of the hypothalamic-pituitary axis and the anatomical relationships with the buccal lobe (BL), a unique gland thought to play a role in reproduction, remains poorly characterized. We present an anatomo-histological analysis of the chimaera Callorhinchus callorynchus using classical histology, immunohistochemistry, and RT-PCR, focus on key neuropeptides related to the control of the reproductive activity in other vertebrates: gonadotropin-releasing hormone (GnRH), secretoneurin (SN), cholecystokinin (CCK), and gonadotropic hormones. The pituitary gland displays clear regionalization into the rostral pars distalis, proximal pars distalis, and neurointermediate lobe. The BL is connected to the posterior telencephalon by paired canals containing a prominent blood vessel and bundles of neuropeptidergic fibers. Gonadotropin-releasing hormone-immunoreactive nerve cell bodies and fibers were identified in the posterior telencephalon using two antisera, with fibers projecting to the proximal pars distalis of the pituitary and the BL. Secretoneurin-immunoreactive neuronal somata and fibers were observed in the posterior telencephalon and hypothalamus, and SN-immunoreactive cells were also present within the pituitary and BL. Cholecystokinin-immunoreactive neuronal elements were detected in the hypothalamus, while CCK-immunoreactive cells were present in the pituitary, and a subset of fibers extending into the BL. RT-PCR analyses revealed the presence of Fshb and Fhb transcripts in the pituitary and BL, with a stronger apparent signal in the BL. These observations provide anatomical evidence for direct neuropeptidergic innervation of both the pituitary and BL and indicate that the BL is associated with gonadotropin subunit gene expression in C. callorynchus. This new anatomical framework of the hypothalamus-pituitary-BL axis identifies two new pathways: direct GnRH and CCK innervation, and local SN-mediated autocrine/paracrine signaling.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pituicyte-derived TGFβ2 regulates Col15a1 expression in pericytes of the rat posterior pituitary. 垂体源性tgf - β2调节大鼠垂体后叶周细胞Col15a1的表达。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-06-03 DOI: 10.1007/s00441-026-04077-2
Takashi Nakakura, Takehiro Tsukada, Takeshi Suzuki
{"title":"Pituicyte-derived TGFβ2 regulates Col15a1 expression in pericytes of the rat posterior pituitary.","authors":"Takashi Nakakura, Takehiro Tsukada, Takeshi Suzuki","doi":"10.1007/s00441-026-04077-2","DOIUrl":"10.1007/s00441-026-04077-2","url":null,"abstract":"<p><p>The posterior lobe (PL) of the pituitary contains a specialized neurovascular junction, where neurosecretory axon terminals closely associate with fenestrated capillaries to enable efficient hormone release into the circulation. The neurosecretory axon terminals and the fenestrated capillaries are supported by an outer basement membrane (BM) and an inner BM, respectively. Although BMs are critical structural components of this junction, their molecular composition and regulatory mechanisms remain poorly understood. We previously demonstrated that COL15A1, the α1 chain of collagen XV, localizes to the BMs surrounding fenestrated capillaries in the anterior lobe of the rat pituitary. In the present study, we examined the localization and regulation of COL15A1 in the rat PL. Immunohistochemical analyses revealed that COL15A1 is localized to the inner BMs of fenestrated capillaries. Combined in situ hybridization and immunohistochemistry demonstrated that Col15a1 is predominantly expressed in NG2-positive pericytes. Water deprivation, which induces arginine vasopressin (AVP) secretion, significantly decreased Col15a1 expression in the PL, whereas AVP stimulation did not affect its expression in primary cultured posterior and intermediate lobe (PIL) cells. We also found that TGFβ2 is produced by S100β-positive pituicytes and TGFβ receptor II is localized to NG2-positive pericytes in the PL. Furthermore, TGFβ2 induces Col15a1 expression in primary cultured PIL cells via TGFβ receptor II and SMAD2 signaling. Collectively, our results identify collagen XV as a key component of the inner BMs surrounding fenestrated capillaries and demonstrate that pericytes orchestrate the structural and functional organization of the neurovascular junction in the PL.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Olfactory coding in honeybees. 更正:蜜蜂的嗅觉编码。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-27 DOI: 10.1007/s00441-026-04065-6
Marco Paoli, Giovanni C Galizia
{"title":"Correction to: Olfactory coding in honeybees.","authors":"Marco Paoli, Giovanni C Galizia","doi":"10.1007/s00441-026-04065-6","DOIUrl":"10.1007/s00441-026-04065-6","url":null,"abstract":"","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell alignment on novel polymeric micro-hollow fiber membranes for neural and musculoskeletal tissue engineering. 神经和肌肉骨骼组织工程用新型聚合物微中空纤维膜的细胞排列。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-23 DOI: 10.1007/s00441-026-04075-4
Scott J Allan, David R Jenkins, Anna Osborne, Rachael Wood, Georgios Mikalef, Cinzia Amieni, Luca Adly Megalaa Shokralla, Zoe Schofield, Ivan Wall, Eric Hill, Marianne J Ellis, Patricia Perez Esteban
{"title":"Cell alignment on novel polymeric micro-hollow fiber membranes for neural and musculoskeletal tissue engineering.","authors":"Scott J Allan, David R Jenkins, Anna Osborne, Rachael Wood, Georgios Mikalef, Cinzia Amieni, Luca Adly Megalaa Shokralla, Zoe Schofield, Ivan Wall, Eric Hill, Marianne J Ellis, Patricia Perez Esteban","doi":"10.1007/s00441-026-04075-4","DOIUrl":"10.1007/s00441-026-04075-4","url":null,"abstract":"<p><p>Precise positioning and alignment of specific cell types, such as those in the central nervous system and the muscular system, is essential for their functional integration, their migration, and proliferation in vivo. Cell alignment in physiologically relevant tissue models and constructs is challenging to reproduce in vitro unless a three-dimensional scaffold is used. This study demonstrates that cell alignment can be guided quickly, inexpensively, and efficiently using polymeric micro-hollow fiber membranes. These micro-hollow fiber membranes are fabricated via single orifice wet spinning from biocompatible polymers-polystyrene and polycaprolactone. The physicochemical characterization of the micro-hollow fiber membranes confirmed their unique architecture, presenting a special patterning on their outer surface. To establish their potential as a platform for cell alignment via contact guidance, the viability, and degree of alignment of relevant cell lines were evaluated when cultured on the micro-hollow fiber membranes. NG108-15, olfactory ensheathing cells and SH-SY5Y cells were used with the aim to simulate the microspatial distribution of cells within the spinal cord, and C2C12 myoblasts were selected to mimic the highly organized structure seen in muscle tissue. Moreover, differentiation of SH-SY5Y cells was successfully induced while cells remained aligned with respect to the micro-HFM's axis. The degree of alignment in all cases was quantified via image analysis in combination with the Fast Fourier Transform algorithm method. This work establishes a platform with very particular micro-topographical features that can be employed to direct growth, orientation, and even differentiation of various cell types for tissue engineering and in vitro modelling.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications. 过渡到胎牛无血清培养提高肾近端小管细胞的生物能量学和允许药理学应用。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-23 DOI: 10.1007/s00441-026-04072-7
Thomas K van der Made, Pim Cleijpool, Polly Paul, Devon A Barnes, Stefan Oswald, Bonnie C Broeksma, Quentin Faucher, Silvia M Mihăilă, Rosalinde Masereeuw
{"title":"Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications.","authors":"Thomas K van der Made, Pim Cleijpool, Polly Paul, Devon A Barnes, Stefan Oswald, Bonnie C Broeksma, Quentin Faucher, Silvia M Mihăilă, Rosalinde Masereeuw","doi":"10.1007/s00441-026-04072-7","DOIUrl":"10.1007/s00441-026-04072-7","url":null,"abstract":"<p><p>Proximal tubule in vitro systems are important tools in pre-clinical drug development, providing insights into drug disposition and safety. Cells are often cultured in medium containing fetal calf serum (FCS); however, FCS addition is not physiologically relevant for cells of human origin. Here, in vitro cultures of human kidney proximal tubule cells were transitioned to FCS-free medium. The impact of FCS-free medium on maturation and maintenance for multiple passages of commonly used conditionally immortalized proximal tubule epithelial cells overexpressing the pharmacologically-relevant organic anion transporter 1 (ciPTEC-OAT1) was evaluated. This transport protein is lost upon isolation and in vitro culture of tubule cells, and due to its clinical relevance, an OAT1 expressing cell line was chosen. Supplementation of FCS-free medium with human platelet lysates supported longer-term cell growth. OAT1-mediated fluorescein transport was sensitive to probenecid inhibition under both conditions, although intracellular fluorescein accumulation was reduced in FCS-free cultures. KEGG and GO enrichment analysis of differentially expressed genes revealed that inflammatory response and HIF-1 signaling were downregulated, whereas cell adhesion and ATP-binding cassette transporter genes were upregulated in FCS-free cultures. Interestingly, an increase in bioenergetic profile was observed for ciPTEC-OAT1 cultured in optimized FCS-free medium. Furthermore, in 3D bioengineered kidney tubule cultures, supplementation with an increased concentration of human platelet lysates lead to improved cell viability and fiber coverage. To conclude, we highlighted significant efforts and strategies in transitioning FCS-containing to FCS-free medium for ciPTEC-OAT1 cultures.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The subcellular distribution of methionine sulfoxide reductase A in mouse and human tissues. 蛋氨酸亚砜还原酶A在小鼠和人体组织中的亚细胞分布。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-18 DOI: 10.1007/s00441-026-04069-2
Hans Agricola, Thomas Lesser, Reinhard Wetzker
{"title":"The subcellular distribution of methionine sulfoxide reductase A in mouse and human tissues.","authors":"Hans Agricola, Thomas Lesser, Reinhard Wetzker","doi":"10.1007/s00441-026-04069-2","DOIUrl":"10.1007/s00441-026-04069-2","url":null,"abstract":"<p><p>Among all known repair enzymes, methionine sulfoxide reductase A (MsrA) plays a key role in protecting against oxidative stress and its damaging effects. The enzyme is ubiquitously expressed in eukaryotic cells and different splice variants of the MsrA gene have been shown to permit the specific prevalence of the protein in different cell organelles. Here, we present novel insights in the intracellular localization of MsrA in selected samples from mouse and human tissue. Using immunocytochemical techniques at both the light and electron microscopic levels, we show incidence of MsrA in human oral mucosa cells, predominantly in the cell nucleus. In addition, the enzyme has been localized in mitochondria of mouse liver and kidney cells, in the cytoplasm of retina cells, and in the endoplasmic reticulum of glandular cells. Overall, the results indicate a correlation between the generation of reactive oxygen species (ROS) and the expression level of MsrA in subcellular compartments of the tissues examined.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells. 破坏三阴性乳腺癌的致癌信号:Cx43、Pyk2和Src在MDA-MB-231细胞中的相互作用
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-13 DOI: 10.1007/s00441-026-04074-5
Li Zheng, Gaelle Spagnol, Paras Gupta, Paul L Sorgen
{"title":"Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells.","authors":"Li Zheng, Gaelle Spagnol, Paras Gupta, Paul L Sorgen","doi":"10.1007/s00441-026-04074-5","DOIUrl":"10.1007/s00441-026-04074-5","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) lacks targeted therapies and is driven by dysregulated signaling networks that promote migration, invasion, and survival. Connexin43 (Cx43), a gap junction protein essential for maintaining normal mammary epithelial homeostasis, becomes aberrantly phosphorylated and mislocalized in breast cancer, contributing to disease progression. Because the tyrosine kinases Pyk2 and Src regulate Cx43 and multiple pro-tumorigenic pathways, we investigated whether their combined inhibition could suppress malignant behaviors in TNBC. In MDA-MB-231 cells, the Pyk2 inhibitor PF4618433 and Src inhibitor Saracatinib modestly reduced metabolic activity at high concentrations; however dual treatment produced a dose-dependent and synergistic reduction in viability. In migration and invasion assays, each inhibitor reduced motility, however dual inhibition produced the strongest suppression. Cx43 knockdown impaired baseline migration and invasion and altered the response to Pyk2/Src inhibition, indicating that Cx43 modulates sensitivity to these agents. PF4618433 increased Cx43 plaque formation without changing total protein levels. Mechanistically, Pyk2 inhibition reduced phosphorylation of Cx43 at Y265 and decreased levels of TAZ, p-Erk1/2, p130Cas, and Notch1, whereas Src inhibition only reduced p-Erk1/2. Dual treatment did not further decrease these signaling nodes but nonetheless produced stronger functional inhibition of viability and motility, and the shared regulation of p-Erk1/2 by Pyk2 and Src may help explain how compensatory Pyk2 activation limits the effectiveness of Src-targeted therapies. Together, these findings show that coordinated Pyk2 and Src inhibition restores Cx43 organization and disrupts multiple malignant traits in TNBC cells, supporting this combination as a promising therapeutic strategy.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional spatial organization of antennal hair plate sensilla and their development in crickets. 蟋蟀触角毛板感受器的功能空间组织及其发育。
IF 3.1 3区 生物学
Cell and Tissue Research Pub Date : 2026-05-08 DOI: 10.1007/s00441-026-04073-6
Hui Lyu, Hiroto Ogawa
{"title":"Functional spatial organization of antennal hair plate sensilla and their development in crickets.","authors":"Hui Lyu, Hiroto Ogawa","doi":"10.1007/s00441-026-04073-6","DOIUrl":"10.1007/s00441-026-04073-6","url":null,"abstract":"<p><p>Antennae of insects are essential mechanosensory organs that facilitate active tactile exploration and spatial navigation. Hair plate sensilla at the base of the antenna flagellum provide proprioceptive inputs to detect the antennae's position. In hemimetabolous insects, such as crickets, the first instar immediately after hatching also possesses antennae; however, the developmental dynamics and spatial organization of antennal hair plates remain poorly understood. We present a comprehensive three-dimensional analysis of the antennal hair plates in crickets (Gryllus bimaculatus) across developmental stages, from the first instar to the adult stage. We demonstrated that hair plate sensilla were present from the first instar and maintained a highly stereotyped spatial arrangement throughout development. Three-dimensional quantification revealed that new sensilla added during molting were formed at specific sites within the hair plate clusters that had existed at the previous stage, maintaining the spatial pattern despite the substantial growth of the antenna. Multidimensional analyses indicated that the spatial arrangement of sensilla was consistent across individuals, suggesting that their organization was under genetic control. Anterograde labeling of sensory afferents showed that sensory neurons in the hair plates converged their axons, extended axon collaterals into the ipsilateral region of the antennal mechanosensory and motor center, and ultimately projected to the subesophageal ganglion. There was no apparent difference in the projection sites among the hair plates, suggesting no clear evidence of topographic organization. Our findings highlight the conserved spatial organization of hair plate sensilla in crickets, suggesting a robust proprioceptive system that provides reliable feedback on antennal position throughout development.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"404 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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