Frontiers in Cell and Developmental Biology最新文献

{"title":"Human acellular amniotic membrane loaded with hair follicle-derived cells promotes wound repair and appendage-like structure formation.","authors":"Yanxin Jiang, Zhongwen Hou, Xichao Jian, Zeyao Tang, Yan Zhou, Xing Hu, Chengliang Deng, Shune Xiao","doi":"10.3389/fcell.2026.1947836","DOIUrl":"10.3389/fcell.2026.1947836","url":null,"abstract":"<p><strong>Background: </strong>Deep skin injuries often heal with scarring and lack skin appendage regeneration, posing a significant clinical challenge. This study aimed to develop an hAAM-based combinatorial strategy for co-delivery of human hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) to full-thickness skin wounds, and to evaluate its effects on wound repair and appendage-like structure formation.</p><p><strong>Methods: </strong>hAAM was prepared and characterized. HFSCs and DPCs were isolated from human hair follicles and identified. The composite construct (hAAM + HFSCs + DPCs) was applied to full-thickness skin wounds in nude mice. Wound healing rates were monitored. Histological and immunohistochemical analyses were performed to assess re-epithelialization, collagen deposition, the presence of CD31-positive vascular structures, cell proliferation, fibrosis-related markers, and morphological features suggestive of appendage-like structures.</p><p><strong>Results: </strong>The hAAM scaffold co-loaded with HFSCs and DPCs was associated with accelerated wound closure, tissue repair, and altered expression of fibrosis-associated markers, including TGF-β and α-SMA, together with altered collagen deposition. The treatment was also associated with the appearance of PPAR-γ-positive structures with morphological features resembling sebaceous glands, as well as epithelial bud-like structures morphologically suggestive of early follicular development, in a subset of specimens. Although these morphological observations are preliminary and require further characterization with additional lineage-specific markers, they represent preliminary morphological observations of appendage-like structures.</p><p><strong>Conclusion: </strong>The hAAM scaffold co-loaded with HFSCs and DPCs was associated with accelerated wound closure, tissue repair, and altered extracellular matrix remodeling in a murine full-thickness wound model. Structures with morphological features resembling sebaceous glands and epithelial bud-like structures suggestive of early follicular development were observed in some samples; however, their cellular identity, maturity, and functionality remain to be determined. Further lineage-specific characterization and long-term functional studies are required to establish whether this strategy can promote appendage-like structure formation and functional skin restoration.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1947836"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215384","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":"Cellular remodeling of lipedema affected subcutaneous adipose tissue.","authors":"Sabrina Gohlke, Francisco Garcia-Carrizo, Robin Upmeyer, Tim J Schulz","doi":"10.3389/fcell.2026.1893552","DOIUrl":"10.3389/fcell.2026.1893552","url":null,"abstract":"<p><p>A progressive disease, lipedema is characterized by bilaterally symmetrical and disproportional accumulation of subcutaneous adipose tissue (SAT) in the extremities, leading to severe pain, inflammation, and mobility issues. Lipedema predominantly affects women in all stages of life and treatment options are currently limited as patients' conditions can only be improved to a limited extent by diet or exercise. The pathogenesis of lipedema remains poorly understood and a reliable diagnostic marker is currently missing. Disease progression is marked by stage-dependent morphological adipose tissue changes, such as adipocyte hypertrophy and stage-dependent fibrosis, accompanied by an elevated proportion of anti-inflammatory macrophages. The molecular mechanisms regulating these compositional and structural changes in adipose tissue, and to what extent this altered response is cause or consequence of the disease, remain unclear. Therefore, the analysis of disease-related changes, with a focus on the cellular dynamics and tissue composition changes may help to distinguish lipedema more reliably from adiposity-related comorbidities.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1893552"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215413","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":"Dynamic increases in p53 expression suppress human myoblast differentiation.","authors":"Ingrid R Aragon, Neha Patole, Ajay Vachanaram, Avram Liban, Colin Hogendorn, Ulas Ozkurede, Feng Feng, Darko Bosnakovski, Eric Batchelor, Julia C Liu","doi":"10.3389/fcell.2026.1844660","DOIUrl":"10.3389/fcell.2026.1844660","url":null,"abstract":"<p><p>Skeletal muscle maintenance and regeneration are highly regulated by cell fate decisions made by muscle stem cells and their progeny, myoblasts. Although the transcription factor p53 is well known for its role in cellular stress responses, cell cycle regulation, and tumor prevention, emerging evidence suggests that p53 also plays a critical role in determining whether myoblasts differentiate into muscle fibers or remain single cells that re-enter quiescence to replenish the satellite cell pool. Most previous studies, however, have relied on static, population-level measurements of p53, leaving its dynamic real-time behavior in individual myoblasts largely unexplored. In this study, we use single cell time-lapse microscopy to investigate temporal patterns of p53 activity in fluorescently-tagged immortalized human myoblasts induced to differentiate. We find that cells in which p53 levels increase more quickly and accumulate to higher amplitudes tend to remain single cells rather than differentiate and fuse into myofibers. Understanding how p53 dynamics influence muscle cell fate may provide fundamental insights into muscle maintenance, regeneration, and degenerative disease.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1844660"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215432","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":"Serum exosomal DDX17 in the diagnosis and action mechanism of hepatocellular carcinoma.","authors":"Defa Huang, Minghong Zhao, Meijin Liu, Tao Chen, Zihao Chen, Yuhuan Xie, Haiyang Yu, Shuqian Zhong, Junyun Huang, Dingyu Rao","doi":"10.3389/fcell.2026.1897138","DOIUrl":"10.3389/fcell.2026.1897138","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore DDX17 protein expression as a diagnostic biomarker of hepatocellular carcinoma (HCC) and its roles in the occurrence and development of HCC.</p><p><strong>Methods: </strong>The proteomics sequencing method was applied to study nine samples of exosomes separated from HCC tissues and corresponding normal non-cancerous tissues. We also performed nanoflow cytometry analysis of DDX17 expression in serum-derived exosomes from 102 HCC patients, 58 persons with liver cirrhosis (LC), and 80 healthy donors (HDs). The feasibility of DDX17 as a diagnostic and prognostic biomarker was evaluated using receiver operating characteristic (ROC) curves. The effects of HCC-derived exosomal DDX17 on LX-2 cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated through cell proliferation, colony formation, wound healing, transwell migration, and western blotting assays.</p><p><strong>Results: </strong>We found that exosomes produced by HCC cells had much higher levels of DDX17 than those produced by the adjacent non-cancerous tissues. ROC analysis showed that exosomal DDX17 has a strong ability to distinguish HCC with both high sensitivity and high specificity. If the exosomal DDX17 result is negative, then we expect it to be a new kind of diagnostic biomarker. Moreover, we observed that DDX17-positive exosome subtypes isolated from the HepG2 cell line increased cell proliferation, migration, invasion, and EMT in the LX-2 cell line.</p><p><strong>Conclusion: </strong>DDX17-positive exosomes are potential diagnostic biomarkers of HCC and are expected to promote tumor growth, migration, invasion, and EMT.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1897138"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215416","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":"Actin disruption is associated with altered YAP/TAZ-responsive transcription and reduced migration during palatal shelf elevation.","authors":"Yang Bai, Jiarong Liu, Siqi Tang, Yuxin Zhang, Chang Liu, Fangchun Chen, Xiaoming Wang, Xiaoxiao Pang","doi":"10.3389/fcell.2026.1962374","DOIUrl":"10.3389/fcell.2026.1962374","url":null,"abstract":"<p><strong>Introduction: </strong>Palatal shelf elevation requires coordinated mesenchymal remodeling, but the relationship between actin organization, mechanosensitive transcription, and mesenchymal motility remains incompletely defined. This study examined how actin disruption relates to YAP/TAZ-responsive transcription and palatal mesenchymal behavior.</p><p><strong>Methods: </strong>Primary mouse embryonic palatal mesenchymal cells and E13.5 palate organ cultures were treated with latrunculin A (Lat-A). Actin organization, YAP localization, wound closure, and palatal shelf orientation were assessed. GA-017, a LATS1/2 inhibitor that can activate both YAP and TAZ, was used to examine responses in the Lat-A background. RNA sequencing and reanalysis of public single-cell multiomic and spatial transcriptomic datasets characterized the associated transcriptional programs.</p><p><strong>Results: </strong>Lat-A disrupted filamentous actin, reduced wound closure, and altered YAP localization. Reduced wound closure persisted in the presence of mitomycin. GA-017 partially opposed the Lat-A-associated changes in wound closure and transcription. RNA sequencing identified 674 genes with opposite-direction changes in the Lat-A-versus-control and Lat-A-plus-GA-017-versus-Lat-A comparisons, including Ccn1, Ccn2, Ankrd1, and Amotl2. In organ culture, Lat-A was associated with reduced F-actin, YAP, CCN1, and CCN2 signals and abnormal palatal shelf orientation. Public datasets provided complementary evidence for the developmental expression and spatial overlap of YAP/TEAD-, CCN-, actin-, and migration-related programs.</p><p><strong>Discussion: </strong>These findings link actin disruption to altered LATS-sensitive YAP/TAZ-responsive transcription and reduced palatal mesenchymal wound closure during palatal elevation. CCN1 and CCN2 are candidate components of this response.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1962374"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215406","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":"Dynamic phosphorylation of DGCR8 regulates embryonic stem cell differentiation and microprocessor function.","authors":"Ka Weng Leong, Lawrence Mok, Karen Gu, Jonathan S Oakhill, Mark M W Chong","doi":"10.3389/fcell.2026.1918038","DOIUrl":"10.3389/fcell.2026.1918038","url":null,"abstract":"<p><p>The Microprocessor complex, minimally composed of DROSHA and DGCR8, is ubiquitously required for microRNA biogenesis. It also regulates the balance between pluripotency and differentiation through mRNA alternative splicing and mRNA cleavage. However, how these various activities are regulated remains incompletely understood. Both DROSHA and DGCR8 are phosphoproteins, and phosphorylation has been reported to influence their molecular functions. In this study, we identified residues in DGCR8 by mass spectrometry that were differentially phosphorylated in mouse embryonic stem cells (mESCs) before and after differentiation into neuronal cells. This included S95 that exhibited greater phosphorylation in undifferentiated cells, and S238 that exhibited greater phosphorylation in differentiated cells. By means of CRISPR/Cas9-mediated genome editing of the endogenous <i>Dgcr8</i> gene, we generated a homozygous S95A mESC clone and a heterozygous S238A/- mESC clone. Both mutants retained an mESC phenotype but exhibited altered Microprocessor-dependent functions and differentiation outcomes. When directed toward the neuronal lineage, the S238A/- mutant displayed elevated mRNA expression of neuronal progenitor markers even after 10 days, while both S95A and S238A/- mutants failed to generate cardiomyocytes in embryoid body differentiation cultures. Furthermore, MEK1/2 inhibition with a highly selective inhibitor partially phenocopied the transcriptional effects of S95A in mESCs, consistent with a potential contribution of ERK/MAPK signaling for S95 phosphorylation. Together, these findings support a role for site-specific DGCR8 phosphorylation in modulating Microprocessor-dependent processes and differentiation in mESCs, establishing DGCR8 phosphorylation as an important regulatory mechanism in the regulation of Microprocessor activity, especially for stem cell differentiation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918038"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215370","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":"Mechanistic study on components of <i>Angelica Pubescens-Taxillus Chinensis</i> in improving compression-induced intervertebral disc degeneration via piezo1/NF-κB signaling axis.","authors":"Fei Yang, Chaoqun Feng, Guangye Li, Junwen Deng, Yunchuan Gou, Bingyi Yang, Ying Zhang, Xin Zhou, Chuan Leng, Maoyin Luo, Rigao Chen, Xiaohong Fan","doi":"10.3389/fcell.2026.1935597","DOIUrl":"10.3389/fcell.2026.1935597","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Abnormal mechanical load is a critical risk factor for intervertebral disc degeneration (IVDD), and nucleus pulposus (NP) cell senescence is a core pathogenic mechanism in IVDD. Piezo1 is a mechanosensitive ion channel, whereas the NF-κB pathway promotes cellular senescence. The classical formula Duhuo Jisheng decoction has shown potential benefits in IVDD-related conditions, and its core herbal pair &lt;i&gt;Angelica Pubescens-Taxillus Chinensis&lt;/i&gt; accounting for its pivotal therapeutic effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to identify the optimal concentration ratio of the &lt;i&gt;Angelica Pubescens-Taxillus Chinensis&lt;/i&gt; component-based Chinese medicine (CBCM) for attenuating compression-induced NP cell senescence and elucidate its molecular mechanism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;An &lt;i&gt;in vitro&lt;/i&gt; NP cell senescence model was established using 1.0 MPa compression. Nine CBCM combinations were defined using an L9 (3&lt;sup&gt;3&lt;/sup&gt;) orthogonal design. A CCK-8 assay was used to screen the optimal and suboptimal combinations. Subsequently, the effect of CBCM on senescence was evaluated using senescence-associated β-galactosidase staining, Western blotting of senescence-related proteins, and qRT-PCR analysis of senescence-associated secretory phenotype factors. Additionally, the impact of CBCM on the Piezo1 and NF-κB pathways was analyzed through Western blotting, qRT-PCR, and immunofluorescence double staining. The underlying mechanism was confirmed by rescue experiments employing a Piezo1 agonist and antagonist, as well as p65 knockdown and overexpression. &lt;i&gt;In vivo&lt;/i&gt;, a rat tail disc compression-induced IVDD model was established. The CBCM was administered intraperitoneally. IVDD was evaluated via X-ray, MRI, and histology. Molecular mechanisms underlying senescence, ECM degradation, and the Piezo1/NF-κB axis were analyzed by ELISA and Western blotting. Molecular docking was performed to further validate plausible interactions of CBN, OST, and QR with Piezo1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compression effectively induced NP cell senescence and activated Piezo1 expression and NF-κB signaling. The CBCM concentration ratio that optimally suppressed senescence markers was quercetin at 50 μM, osthole at 6.25 μM, and columbianadin at 12.5 μM. Mechanistically, the optimized CBCM inhibited Piezo1 expression, NF-κB activation, and p65 nuclear translocation. Both p65 knockdown and Piezo1 inhibition mimicked CBCM's anti-senescent effects, whereas p65 overexpression or Piezo1 agonism reversed these protective effects. These &lt;i&gt;in vitro&lt;/i&gt; findings were corroborated in a rat tail compression model of IVDD. Molecular docking offered computational evidence supporting the potential direct binding of CBN, OST, and QR with Piezo1 and proteins involved in the NF-κB signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These findings suggest that the optimal &lt;i&gt;Angelica Pubescens-Taxillus Chinensis&lt;/i&gt; CBCM attenuat","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1935597"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215379","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":"Integrated toxicogenomic and single-nucleus transcriptomic analyses prioritize SDHB and NDUFAB1 in mitochondrial respiration-associated remodeling during cisplatin-induced acute kidney injury.","authors":"Dianjie Zeng, Yunhui He, Huijie Hu, Xuzheng Wang, Changkun Huang","doi":"10.3389/fcell.2026.1939354","DOIUrl":"10.3389/fcell.2026.1939354","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin-induced acute kidney injury (Cis-AKI) is a multifactorial nephrotoxic syndrome involving proximal tubular injury, oxidative and inflammatory stress, mitochondrial dysfunction, metabolic disturbance, and regulated cell death. However, the molecular targets linking cisplatin-associated toxicogenomic changes to AKI remain incompletely characterized.</p><p><strong>Methods: </strong>We integrated network toxicology, transcriptomic analysis, single-nucleus RNA sequencing, and <i>in vitro</i> experiments to investigate candidate molecular targets in Cis-AKI. Cisplatin-associated toxicogenomic genes were intersected with AKI-related genes, and the shared candidates were analyzed using functional enrichment, protein-protein interaction networks, CytoHubba, and MCODE. Prioritized genes were further examined in a cisplatin-induced mouse Acute kidney injury transcriptomic dataset, a human AKI kidney single-nucleus dataset, proximal tubular pseudotime analysis, and cisplatin-treated BUMPT proximal tubular cells. NicheNet analysis, knockout phenotype annotation, miRNA prediction, candidate compound screening, and molecular docking were also performed.</p><p><strong>Results: </strong>A total of 214 shared genes were identified between the cisplatin-associated and AKI-related gene sets. These genes were mainly enriched in cellular respiration, electron transport, oxidoreductase activity, respiratory-chain complexes, and oxidative phosphorylation. Network analysis prioritized SDHB and NDUFAB1 within the respiration-associated gene network. In the cisplatin-induced mouse AKI dataset, Aco2, Aco1, Sdhb, and Aldh2 were significantly upregulated under stringent criteria, whereas additional respiration- and metabolism-related genes, including Ndufab1, met a secondary differential expression threshold. Human single-nucleus analysis revealed distinct cell-type-specific expression patterns of SDHB and NDUFAB1, with increased SDHB and decreased NDUFAB1 expression in proximal tubular cells. Pseudotime analysis showed a more pronounced late-stage increase in SDHB, whereas NDUFAB1 displayed weaker dynamics. In cisplatin-treated BUMPT cells, Havcr1 and Lcn2 were increased, Bcl2 was decreased, and Casp3 was increased. Among the selected candidate genes, Sdhb, Aco2, Aldh2, Ndufs2, and Uqcrc1 were upregulated, whereas Ndufab1 showed a modest decrease. NicheNet analysis further suggested that TGFB1-related signaling may contribute to proximal tubular transcriptional remodeling.</p><p><strong>Conclusion: </strong>This study prioritizes SDHB and NDUFAB1 within a respiration-associated gene network in Cis-AKI and demonstrates that they exhibit distinct expression patterns during proximal tubular injury. These findings highlight respiration-associated remodeling and proximal tubular state transition in cisplatin-induced kidney injury.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1939354"},"PeriodicalIF":5.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215356","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":"Distinct osteoclast transcriptional states and heterotypic fusion arising from circulating pre-dendritic cells and monocytes.","authors":"Patricia Riedlova, Sabarinadh Chilaka, Shatakshi Sood, John Cole, Cecilia Ansalone, Carl S Goodyear","doi":"10.3389/fcell.2026.1954531","DOIUrl":"10.3389/fcell.2026.1954531","url":null,"abstract":"<p><p>Osteoclasts (OCs) are multinucleated bone-resorbing cells essential for bone remodelling and contribute to pathological bone loss in inflammatory and metabolic bone diseases. Although classically considered to arise from monocyte/macrophage precursors, circulating pre-dendritic cells (pre-DCs) also retain osteoclastogenic potential. However, whether OCs derived from these distinct precursors retain different transcriptional states, and how they interact during fusion, remain unclear. Here, we compared OCs generated from directly isolated circulating monocytes and pre-DCs and investigated how these populations contribute to OC formation and fusion within mixed cultures. RNA sequencing identified 41 genes significantly enriched in pre-DC-derived OCs and 9 in monocyte-derived OCs, while core osteoclastogenic and fusion-associated genes showed no significant differential expression. Gene set enrichment analysis (GSEA) identified distinct precursor-associated transcriptional programmes. Pre-DC-derived OCs were enriched for extracellular matrix organisation, skeletal development, canonical Wnt signalling and immune-regulatory pathways, whereas monocyte-derived OCs were enriched for cell-cycle, proteasomal, lysosomal and innate immune pathways. In mixed cultures, OC output increased with the proportion of pre-DCs, with the greatest OC formation observed in pre-DC-only cultures. Live-cell imaging demonstrated heterotypic fusion, with monocyte-derived precursors observed fusing with established pre-DC-derived multinucleated OCs, whereas exclusively monocyte-derived multinucleated OCs were infrequently observed. These findings indicate that both populations generate OCs with a conserved core transcriptional profile but distinct precursor-associated transcriptional states. Greater pre-DC abundance was associated with increased OC output, and live-cell imaging showed that monocyte-derived cells can be incorporated into pre-DC-derived multinucleated OCs. This heterogeneity may influence OC abundance, multinucleation, and functional properties in inflammatory and metabolic bone diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1954531"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180419","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":"Advances in mechanical force-induced adaptive responses and pathological transition of renal tubular epithelial cells.","authors":"Shilin Li, Yuefeng Cai, Yi Zeng, Zhixia Song, Xisheng Wang","doi":"10.3389/fcell.2026.1981323","DOIUrl":"10.3389/fcell.2026.1981323","url":null,"abstract":"<p><p>Renal tubular epithelial cells (RTECs) reside in a mechanical microenvironment shaped by fluid shear stress, hydrostatic pressure, and cyclic stretch. Under physiological conditions, moderate mechanical stimulation helps maintain normal renal function by regulating cell volume, ion transport, and transcriptional programs. Tubular injury occurs when the intensity or duration of stimulation exceeds physiological tolerance. The balance between protective repair and pathological injury is determined jointly by stimulus intensity, exposure duration, and cellular adaptive capacity. Existing reviews of mechanical stress-induced kidney injury have largely emphasized pathological endpoints. The distinctive contribution of this review is to place the adaptive-to-pathological transition (the threshold at which protective mechanisms fail) and the segmental heterogeneity of tubular mechanoresponses at the center of its framework. We synthesize the molecular mechanisms by which RTECs sense and transduce mechanical signals, with particular emphasis on early adaptive responses including cytoskeletal reorganization, protein quality control, and remodeling of ion homeostasis, and we describe how persistent mechanical stimulation drives the transition from physiological adaptation to pathological injury. We further discuss quantitative and contextual thresholds for this transition, clinically relevant mechanical scenarios beyond classical obstruction, and the phase dependence of mechanosensitive therapeutic targets such as YAP/TAZ. Current research models and technologies are reviewed together with unresolved questions and future directions. By framing mechanically driven kidney disease as a continuum between adaptation and injury, this synthesis provides a theoretical basis for mechanistic studies and for timing-aware, segment-specific clinical translation in mechanical force-related kidney diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1981323"},"PeriodicalIF":5.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180484","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}