Frontiers in Cell and Developmental Biology最新文献

{"title":"Vesicular trafficking and cell-cell communication in neurodevelopment and neurodegeneration.","authors":"Salma Amin, Elena Taverna","doi":"10.3389/fcell.2025.1600034","DOIUrl":"10.3389/fcell.2025.1600034","url":null,"abstract":"<p><p>Regulation of vesicle biology and trafficking plays a critical role in cell viability. Vesicular trafficking is a process that entails vesicle biogenesis, transport, and sorting of materials such as proteins, enzymes, hormones, and neurotransmitters to different cellular compartments. This phenomenon is especially important in cells of the central nervous system, including neural progenitors, neurons, and glial cell populations, because of their highly polarized architecture. In line with that, disruption in vesicular trafficking during cortical development affects progenitor proliferation and differentiation and leads to brain malformations. On the other hand, neuronal cells require long-range vesicular trafficking to reach distant locations, such as the distal part of the axons, and synaptic vesicles are essential for cell-cell communication. Neurons have high energy demands. Therefore, any malfunction in vesicular trafficking is a trigger to spiraling into neurodegeneration. Here, we give a comprehensive review of the role of intracellular and extracellular vesicles in cortical development and neurodegeneration, and we discuss how trafficking between organelles in specific cell types contributes to brain pathologies. Finally, we highlight the emerging evidence linking disruption in vesicular trafficking to neurological disorders such as Alzheimer's disease, Parkinson's disease, and autism.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1600034"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474525","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":"Skin lamellar bodies: a unique set of lysosome-related organelles.","authors":"Sarmistha Mahanty","doi":"10.3389/fcell.2025.1597696","DOIUrl":"10.3389/fcell.2025.1597696","url":null,"abstract":"<p><p>Skin lamellar bodies (LBs) are crucial for forming and renewing the protective skin barrier, which regulates the body's internal environment and integrity. LB dysfunction is associated with severe disease conditions such as atopic dermatitis, Netherton syndrome and Harlequin ichthyosis, among others. Despite its importance in human physiology, the intracellular origin and biogenesis mechanism of LBs remain largely unknown. LBs are lysosome-related organelles (LRO), a group of cell type-specific organelles having unique structures, cargo content, and function. Classical LROs such as melanosomes, lung lamellar bodies and Weibel-Palade bodies share overlapped molecular machinery/mechanisms and are co-affected in genetic disorders like Hermansky-Pudlak syndrome (HPS) or Chédiak-Higashi syndrome (CHS). In contrast, LBs contain a diverse array of protein and lipid cargo that are notably different from those found in other LROs, and LBs are not reported to be affected in HPS/CHS. LBs form in an advanced differentiation state of keratinocytes while cells are experiencing high ions and low nutrients in their exterior, the plasma membrane (PM) undergoing modifications, and intracellular organelles starting to disappear. This article discusses atypical conditions of LB biogenesis in comparison to classical LROs, which may potentially guide future research on LB biogenesis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1597696"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474524","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":"17β-estradiol maintains extracellular matrix homeostasis of nucleus pulposus cells by activating p70 S6K1 signaling pathway.","authors":"Tao Liu, Zhaohui Li, Wei Zhang, Xuzhao Guo, Guobin Liu, Dalong Yang, Sidong Yang","doi":"10.3389/fcell.2025.1564458","DOIUrl":"10.3389/fcell.2025.1564458","url":null,"abstract":"<p><strong>Background: </strong>Estrogen can inhibit the apoptosis of nucleus pulposus cells (NPCs) through the PI3K/AKT/mTOR signaling pathway. However, the downstream of mTOR signaling pathway remains elusive. This study investigates the effect of 17β-estradiol (E2) on intervertebral disc degeneration (IVDD) through the p70 S6K1 signaling pathway, downstream of mTOR.</p><p><strong>Methods: </strong>The IVDD model of rats was established by needle puncture and bilateral ovariectomy. Fifteen Sprague-Dawley rats were randomly assigned to the following three groups: (A) Sham surgery group (Sham); (B) Bilateral ovariectomy, 21G needle puncture and carrier injection (OVX + veh); (C) Bilateral ovariectomy, 21G needle puncture, E2 supplementation (OVX + E2). The degree of IVDD was evaluated by X-ray, magnetic resonance imaging (MRI), hematoxylin and eosin (H&E), and Safranin O-Fast Green staining. The expression levels of target protein p70S6K1 and its phosphorylated products were detected by immunohistochemistry (IHC). Finally, Western blot analysis and immunofluorescence staining were used to investigate the effect of E2 on the p70 S6K1 signaling pathway <i>in vitro</i>.</p><p><strong>Results: </strong>Histological staining and radiological results showed that E2 supplementation altered signaling, suggesting that it may have a protective effect against IVDD. IHC showed that compared with the Sham and OVX + E2 groups, the level of p70 S6K1 in the OVX + veh group was significantly increased while the expression of phosphorylated products (p-S6) was significantly decreased, suggesting that E2 could inhibit IVDD by activating p70 S6K1 signaling pathway, the downstream of mTOR. Furthermore, cellular immunofluorescence and Western blot showed that E2 can maintain extracellular matrix (ECM) balance and inhibits apoptosis of nucleus pulposus cells (NPCs) by activating the p70 S6K1 signaling pathway.</p><p><strong>Conclusion: </strong>In summary, 17β-estradiol mitigates IVDD progression by maintaining ECM homeostasis and inhibiting NPCs apoptosis through activation of the p70 S6K1 signaling pathway downstream of mTOR.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1564458"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368748","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":"Hedgehog signaling controls astral microtubules and mitotic spindle orientation in neural progenitors and iPSCs.","authors":"Fengming Liu, Anna Medyukhina, Kris M Olesen, Abbas Shirinifard, Hongjian Jin, Lei Li, Marina Mapelli, Khaled Khairy, Young-Goo Han","doi":"10.3389/fcell.2025.1582924","DOIUrl":"10.3389/fcell.2025.1582924","url":null,"abstract":"<p><p>Mitotic spindle orientation is crucial for cell fate determination and tissue organization. Although the intracellular machinery governing spindle orientation is well characterized, whether and how secreted factors, such as morphogens, regulate this process remains poorly understood. This study investigated the role of Hedgehog (HH) signaling in modulating mitotic spindle orientation in neural progenitor cells and in induced pluripotent stem cells (iPSCs). Time-lapse microscopy of cerebral organoids and iPSCs revealed that HH signaling increases the angle of the mitotic spindle relative to the apical surface, prolongs mitosis, and enhances spindle rotation. Mechanistically, HH signaling reduces both the number and the length of astral microtubules, key regulators of spindle orientation. This reduction correlates with increased spindle angle in iPSCs. Furthermore, we show that canonical HH signaling, involving GLI-dependent transcriptional regulation, contributes to these effects. RNA sequencing and gene set enrichment analysis (GSEA) revealed that HH signaling upregulates genes associated with microtubule depolymerization, suggesting a transcriptional mechanism by which HH signaling influences astral microtubule dynamics and, consequently, mitotic spindle orientation. These findings highlight a novel link between a morphogen, transcriptional regulation, and the control of mitotic spindle orientation, with implications for development and tissue homeostasis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1582924"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368749","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":"MSLI-Net: retinal disease detection network based on multi-segment localization and multi-scale interaction.","authors":"Zhenjia Qi, Jin Hong, Jilan Cheng, Guoli Long, Hanyu Wang, Siyue Li, Shuangliang Cao","doi":"10.3389/fcell.2025.1608325","DOIUrl":"10.3389/fcell.2025.1608325","url":null,"abstract":"<p><strong>Background: </strong>The retina plays a critical role in visual perception, yet lesions affecting it can lead to severe and irreversible visual impairment. Consequently, early diagnosis and precise identification of these retinal lesions are essential for slowing disease progression. Optical coherence tomography (OCT) stands out as a pivotal imaging modality in ophthalmology due to its exceptional performance, while the inherent complexity of retinal structures and significant noise interference present substantial challenges for both manual interpretation and AI-assisted diagnosis.</p><p><strong>Methods: </strong>We propose MSLI-Net, a novel framework built upon the ResNet50 backbone, which enhances the global receptive field via a multi-scale dilation fusion module (MDF) to better capture long-range dependencies. Additionally, a multi-segmented lesion localization module (LLM) is integrated within each branch of a modified feature pyramid network (FPN) to effectively extract critical features while suppressing background noise through parallel branch refinement, and a wavelet subband spatial attention module (WSSA) is designed to significantly improve the model's overall performance in noise suppression by collaboratively processing and exchanging information between the low- and high-frequency subbands extracted through wavelet decomposition.</p><p><strong>Results: </strong>Experimental evaluation on the OCT-C8 dataset demonstrates that MSLI-Net achieves 96.72% accuracy in retinopathy classification, underscoring its strong discriminative performance and promising potential for clinical application.</p><p><strong>Conclusion: </strong>This model provides new research ideas for the early diagnosis of retinal diseases and helps drive the development of future high-precision medical imaging-assisted diagnostic systems.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1608325"},"PeriodicalIF":4.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368750","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":"Proteasome caspase-like activity regulates stress granules and proteasome condensates.","authors":"Shirel Steinberger, Julia Adler, Nadav Myers, Yosef Shaul","doi":"10.3389/fcell.2025.1570499","DOIUrl":"10.3389/fcell.2025.1570499","url":null,"abstract":"<p><p>The 20S proteasome maintains cellular protein homeostasis, particularly during stress responses. In a previous study, we identified numerous 20S proteasome substrates through mass spectrometry analysis of peptides generated from cellular extracts degraded by purified 20S proteasome. Many substrates were found to be components of liquid-phase separation, such as stress granules (SGs). Here, we demonstrate the degradation products arise from the caspase-like (CL) proteasomal activity. To investigate the functional implications of CL activity, we generated cell lines devoid of CL function by introducing the PSMB6 T35A mutation. These mutant cells exhibited slower growth rates, heightened sensitivity to stress, and activation of the unfolded protein response (UPR), as indicated by elevated levels of spliced XBP1 (sXBP1) and stress markers. Cells were subjected to arsenite and osmotic stress to assess their responses. Our findings reveal that CL activity is crucial for efficient SG assembly but does not significantly affect SG clearance. Interestingly, in these mutant cells, proteasomes were more cytoplasmic under normal conditions but formed nuclear condensates/granules (PGs) upon NaCl osmotic stress. However, the PGs were unstable and rapidly dispersed. These findings underscore the important role of the proteasome's CL activity in managing stress-induced dynamics of liquid-liquid phase, highlighting its importance in cellular adaptation to proteotoxic and genotoxic stress conditions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1570499"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332768","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":"p90RSK modulates inter-and intracellular signaling in kidney diseases.","authors":"Ling Lin, Kebin Hu","doi":"10.3389/fcell.2025.1593914","DOIUrl":"10.3389/fcell.2025.1593914","url":null,"abstract":"<p><p>The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also named as p90RSK. p90RSK is directly phosphorylated and activated by its immediate upstream mediator extracellular signal-regulated kinase (Erk1/2), followed by activating various signaling pathways through phosphorylating selective downstream substrates. Aberrant induction of p90RSK has been reported in various human diseases including kidney disease suggesting a pathogenic role of p90RSK in these diseases. In response to pathogenic cues, p90RSK not only mediates intracellular signal events leading to cell-specific phenotypes but also modulates intercellular communication impacting the adjacent cellular responses. In this review, we provide an update on the current knowledge regarding the roles of p90RSK-mediated intercellular and intracellular signaling in the pathogenesis and progression of kidney diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1593914"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332767","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":"Lowe Syndrome and Me: a co-creation video series connecting patients, caregivers, and researchers.","authors":"Theresa Haugen, Jennifer L Gallop, Hélène Doerflinger","doi":"10.3389/fcell.2025.1610207","DOIUrl":"10.3389/fcell.2025.1610207","url":null,"abstract":"<p><p>Lowe syndrome (LS) is a rare genetic disorder leading to significant physical and cognitive impairments. Recognizing the need to bridge the gap between researchers and the LS community, a collaborative patient and public involvement (PPI) project, Lowe Syndrome and Me, was initiated. This initiative aimed to foster understanding, improve communication, and strengthen advocacy through a co-created video series. Researchers from the Gurdon Institute (United Kingdom) and caregivers from the Lowe Syndrome Association (United States) collaborated to develop a series of videos capturing the unique perspectives of patients and their families, advocacy group members, and researchers. Participants received video production and scriptwriting training, ensuring authentic representation and shared ownership of the content. The videos were disseminated through social media, research institute and patient group websites in the United States, United Kingdom and France, raising awareness and improving engagement within the LS community. Feedback from participants highlighted high satisfaction, increased understanding of research, and enhanced communication skills. Challenges included geographical barriers and limited participant diversity, but the project successfully fostered reciprocal learning and strengthened advocacy networks. This case illustrates how meaningful PPI can empower patient communities, enhance research relevance, and promote broader public awareness of rare diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1610207"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332765","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":"Immune dysregulation in ulcerative colitis: pathogenic mechanisms and therapeutic strategies of traditional Chinese medicine.","authors":"Xudong Tang, Yilin Huang, Ying Zhu, Yin Xu","doi":"10.3389/fcell.2025.1610435","DOIUrl":"10.3389/fcell.2025.1610435","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized primarily by immune dysregulation. Its pathogenesis involves multiple factors, including dysregulation of T-cell subsets, hypersecretion of pro-inflammatory cytokines, imbalance in the gut microbiota, and disruption of the intestinal barrier. Among T-cell subsets, abnormal activation of Th1 and Th17 cells, in conjunction with Treg dysfunction, significantly amplifies local pro-inflammatory signals. Pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-17, exacerbate apoptosis and disrupt tight junctions (TJs) in intestinal epithelial cells (IECs), thereby creating favorable conditions for invasion by pathogenic bacteria and their metabolites. Intestinal microecological imbalance not only leads to significant alterations in the structure of the bacterial flora but also involves abnormal fluctuations in its metabolites that directly regulate intestinal immune homeostasis, a factor closely associated with the severity of inflammation and prognosis of ulcerative colitis. Recent studies have demonstrated that in the treatment of UC, traditional Chinese medicine (TCM) achieves a multi-target, multi-pathway integrated intervention by regulating immune cell differentiation, balancing inflammatory factor levels, repairing the intestinal epithelial barrier, and remodeling the structure of the bacterial flora. This article reviews the pathogenic mechanisms underlying immune dysregulation in UC and the advances in research on TCM's role in immune regulation, anti-inflammatory repair, and flora modulation, encompassing the mechanisms of action of individual active ingredients and classic TCM compound formulas. Although some studies have preliminarily confirmed TCM's potential to modulate immunity and repair the intestinal barrier, breakthroughs in mechanism analysis, herb standardization, and large-scale validation remain forthcoming. It is anticipated that the unique advantages of TCM will be translated into a more precise therapeutic strategy for UC through modern molecular and systems biology approaches.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1610435"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332764","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":"Editorial: Rehabilitation and regeneration in orthopaedic: from cellular regulation to innovative medical technologies.","authors":"Weidan Wang, Ye Li, Jiannan Li, Weihao Yuan, Dewei Zhao","doi":"10.3389/fcell.2025.1633691","DOIUrl":"10.3389/fcell.2025.1633691","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1633691"},"PeriodicalIF":4.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332763","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}