{"title":"Molecular dynamics of chemotactic signalling orchestrates dental pulp stem cell fibrosis during aging.","authors":"Tianmeng Sun, Qing Zhong, Xiaoyi Yu, Huanyu Luo, Feilong Ren, Cangwei Liu, Peng Chen, Fabian Flores-Borja, Hongchen Sun, Zhengwen An","doi":"10.3389/fcell.2024.1530644","DOIUrl":"10.3389/fcell.2024.1530644","url":null,"abstract":"<p><p>Aging often triggers dental pulp fibrosis, resulting in clinical repercussions such as increased susceptibility to dental infections, compromised tooth vitality, and reduced responsiveness to dental interventions. Despite its prevalence, the precise molecular mechanisms underlying this condition remains unclear. Leveraging single-cell transcriptome analysis from both our own and publicly available datasets, we identified Ccrl2<sup>+</sup> macrophages as particularly vulnerable during the early stages of aging. Notably, dental pulp progenitors with high expression of RARRES2, a unique ligand for CCRL2, facilitate the selective recruitment of a specific macrophage population to the stem cell niches. This process culminates in the formation of the ligand-receptor complex that engages CMKLR1, a receptor broadly expressed across macrophage populations. This interaction drives macrophage activation and expansion through the RARRES2/CCRL2/CMKLR1 axis. Through rigorous experimental validation, we demonstrated that macrophage activation and expansion within stem cell niches lead to increased secretion of proinflammatory factors, promoting dental pulp fibrosis during aging. Our findings uncover the intricate molecular dynamics of dental pulp aging, emphasizing immune microenvironment interactions. This study provides a novel perspective on potential therapeutic strategies for age-related pulp diseases by targeting macrophages and modulating the immune microenvironment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1530644"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046019","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}
Sakhawat Shah, Chun-Mei Shi, Karam Khamis Elgizawy, Wen-Han Yan, Gang Wu, Xiao-Ping Wang, Feng-Lian Yang
{"title":"<i>E3 Siah</i> ubiquitin ligase regulates dichotomous spermatogenesis in <i>Sitotroga cerealella</i>.","authors":"Sakhawat Shah, Chun-Mei Shi, Karam Khamis Elgizawy, Wen-Han Yan, Gang Wu, Xiao-Ping Wang, Feng-Lian Yang","doi":"10.3389/fcell.2024.1507725","DOIUrl":"10.3389/fcell.2024.1507725","url":null,"abstract":"<p><p>Spermatogenesis in Lepidoptera holds significant importance due to its unique process of dichotomous spermatogenesis, yielding eupyrene and apyrene spermatozoa through a complex molecular mechanism. While E3 ubiquitin ligases are known to play vital roles in spermatogenesis across various processes, their functions in dichotomous spermatogenesis remain less known. We utilized the RNAi, biochemical and microscopic procedures to unravel the function of <i>ScE3 Siah</i> in dichotomous spermatogenesis of adult <i>Sitotroga cerealella</i>. In <i>S</i>. <i>cerealella E3</i> ligase <i>Siah</i> predominantly expressed in adult tissues. Knockdown of <i>ScE3 Siah</i> leads to disruptions in testes and sperm morphology, affecting the structure of eupyrene and apyrene sperm bundles and causing defective ultrastructure in eupyrene sperm. This disruption results in a reduction in the number of dichotomous sperms and significantly reduces their motility. Moreover, <i>ScE3 Siah</i> knockdown inhibits the transfer and motility of dichotomous sperm, impacting spermatophore formation in females and ultimately reducing egg production. Understanding the role of <i>ScE3 Siah</i> is not only crucial for comprehending the complex processes involved in dichotomous spermatogenesis and fertilization but also provides an avenue for sustainable pest control management.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1507725"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046016","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}
Hana Mahmutefendić Lučin, Igor Štimac, Marina Marcelić, Matej Skočaj, Berislav Lisnić, Alen Omerović, Ivona Viduka, Barbara Radić, Ljerka Karleuša, Gordana Blagojević Zagorac, Martina Deželjin, Antonija Jurak Begonja, Pero Lučin
{"title":"Rab10-associated tubulation as an early marker for biogenesis of the assembly compartment in cytomegalovirus-infected cells.","authors":"Hana Mahmutefendić Lučin, Igor Štimac, Marina Marcelić, Matej Skočaj, Berislav Lisnić, Alen Omerović, Ivona Viduka, Barbara Radić, Ljerka Karleuša, Gordana Blagojević Zagorac, Martina Deželjin, Antonija Jurak Begonja, Pero Lučin","doi":"10.3389/fcell.2024.1517236","DOIUrl":"10.3389/fcell.2024.1517236","url":null,"abstract":"<p><strong>Introduction: </strong>Cytomegalovirus (CMV) infection reorganizes early endosomes (EE), recycling endosome (RE), and trans-Golgi network (TGN) and expands their intermediates into a large perinuclear structure that forms the inner part of the cytoplasmic assembly complex (AC). The reorganization begins and results with the basic configuration (known as pre-AC) in the early (E) phase of infection, but the sequence of developmental steps is not yet well understood. One of the first signs of the establishment of the inner pre-AC, which can be observed by immunofluorescence, is the accumulation of Rab10. This study aims to investigate whether Rab10-positive domain (Rab10-PD) is expanded during the E phase of infection.</p><p><strong>Methods: </strong>We performed long-term live imaging of EGFP-Rab10 with epifluorescence imaging-enhanced digital holotomographic microscopy (DHTM), confocal imaging of known Rab10 interactors and identification of important Rab10 interactors with the proximity-dependent biotin identification assay (BioID). The accumulation of Rab10-PD was analyzed after knock-down of EHBP1 and Rabin8, two proteins that facilitate Rab10 recruitment to membranes, and after blocking of PI(4,5)P2 by PI(4,5)P2-binding protein domains.</p><p><strong>Results: </strong>Our study shows the gradual expansion of Rab10-PD in the inner pre-AC, the association of Rab10 with EHBP1 and MICAL-L1, and the dependence of Rab10-PD expansion on EHBP1 and PI(4,5)P2 but not Rabin8, indicating the expansion of EE-derived tubular recycling endosome-like membranes in the pre-AC. Silencing of Rab10 and EHBP1 suggests that Rab10-PD expansion is not required for the establishment of the inner pre-AC nor for the expansion of downstream tubular domains.</p><p><strong>Conclusion: </strong>The present work characterizes one of the earliest sequences in the establishment of pre-AC and suggests that subsets of EE-derived tubular membranes may serve as the earliest biomarkers in pre-AC biogenesis. Our study also indicates that the pre-AC biogenesis is complex and likely involves multiple parallel processes, of which Rab10-PD expansion is one. Our experiments, particularly our silencing experiments, show that Rab10 and EHBP-1 do not play a significant role in the later stages of inner pre-AC biogenesis or in the expansion of downstream tubular domains. A more comprehensive understanding of the tubular domain expansion remains to be established.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1517236"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046021","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":"HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.","authors":"Shruti Ghai, Rejina Shrestha, Kuo-Hui Su","doi":"10.3389/fcell.2024.1500880","DOIUrl":"10.3389/fcell.2024.1500880","url":null,"abstract":"<p><p>Heat Shock Factor 1 (HSF1) is a major transcriptional factor regulating the heat shock response and has become a potential target for overcoming cancer chemoresistance. This review comprehensively examines HSF1's role in chemoresistance and its potential as a therapeutic target in cancer. We explore the complex, intricate mechanism that regulates the activation of HSF1, HSF1's function in promoting resistance to chemotherapy, and the strategies used to manipulate HSF1 for therapeutic benefit. In addition, we discuss emerging research implicating HSF1's roles in autophagy, apoptosis, DNA damage repair, drug efflux, and thus chemoresistance. This article highlights the significance of HSF1 in cancer chemoresistance and its potential as a target for enhancing cancer treatment efficacy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1500880"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028504","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}
Martin Anger, Katerina Komrskova, Ahmed Z Balboula, Paolo Rinaudo, Jason G Knott
{"title":"Editorial: Fertilization and early embryogenesis: from research to clinical practice.","authors":"Martin Anger, Katerina Komrskova, Ahmed Z Balboula, Paolo Rinaudo, Jason G Knott","doi":"10.3389/fcell.2024.1547205","DOIUrl":"https://doi.org/10.3389/fcell.2024.1547205","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1547205"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028480","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}
Na Wang, Han Yang, Yelei Chen, Hekun Wang, Chaorui Wang, Jianglin Fan, Yajie Chen, Yinghua Li, Maobi Zhu
{"title":"Formononetin promotes porcine oocytes maturation and improves embryonic development by reducing oxidative stress.","authors":"Na Wang, Han Yang, Yelei Chen, Hekun Wang, Chaorui Wang, Jianglin Fan, Yajie Chen, Yinghua Li, Maobi Zhu","doi":"10.3389/fcell.2024.1520429","DOIUrl":"10.3389/fcell.2024.1520429","url":null,"abstract":"<p><p>Increasing evidence has demonstrated that oxidative stress impairs oocyte maturation and embryonic development. Conventionally, antioxidants have been applied <i>in vitro</i> systems to improve oocyte maturation and blastocyst rates. Formononetin (FMN) is a flavonoid that has been shown to have various pharmacological effects, including antioxidants. In this study, we delved into the impact of FMN, acting as an antioxidant, on the <i>in vitro</i> development of oocytes and blastocysts within the culture system. FMN supplementation at 0.5 μM enhanced the rate of first polar body extrusion and blastocyst formation post parthenogenetic activation. It also increased mitochondrial function and ATP levels, reduced intracellular reactive oxygen species, and elevated intracellular GSH levels in both oocytes and embryos. Moreover, FMN significantly decreased autophagy and apoptosis levels in blastocyst cells, potentially via regulation of the Nrf2/Keap1 pathway. This is the first study to report that FMN supplementation benefits the <i>in vitro</i> culture of oocytes and early embryo development, potentially by regulating oxidative stress, mitochondrial function, and autophagy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1520429"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028498","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}
Mirella Pastore, Alessia Giachi, Elena Spínola-Lasso, Fabio Marra, Chiara Raggi
{"title":"Organoids and spheroids: advanced <i>in vitro</i> models for liver cancer research.","authors":"Mirella Pastore, Alessia Giachi, Elena Spínola-Lasso, Fabio Marra, Chiara Raggi","doi":"10.3389/fcell.2024.1536854","DOIUrl":"10.3389/fcell.2024.1536854","url":null,"abstract":"<p><p>Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional <i>in vivo</i> animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven the development of advanced <i>in vitro</i> models. Spheroids and organoids have emerged as powerful tools due to their ability to replicate tumor microenvironment and facilitate preclinical drug development. Spheroids are simpler 3D culture models that partially recreate tumor structure and cell interactions. They can be used for drug penetration studies and high-throughput screening. Organoids derived from stem cells or patient tissues that accurately emulate the complexity and functionality of liver tissue. They can be generated from pluripotent and adult stem cells, as well as from liver tumor specimens, providing personalized models for studying tumor behavior and drug responses. Liver organoids retain the genetic variability of the original tumor and offer a robust platform for high-throughput drug screening and personalized treatment strategies. However, both organoids and spheroids have limitations, such as the absence of functional vasculature and immune components, which are essential for tumor growth and therapeutic responses. The field of preclinical modeling is evolving, with ongoing efforts to develop more predictive and personalized models that reflect the complexities of human liver cancer. By integrating these advanced <i>in vitro</i> tools, researchers can gain deeper insights into liver cancer biology and accelerate the development of novel treatments.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1536854"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028429","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":"Color fundus photograph-based diabetic retinopathy grading via label relaxed collaborative learning on deep features and radiomics features.","authors":"Chao Zhang, Guanglei Sheng, Jie Su, Lian Duan","doi":"10.3389/fcell.2024.1513971","DOIUrl":"10.3389/fcell.2024.1513971","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic retinopathy (DR) has long been recognized as a common complication of diabetes, making accurate automated grading of its severity essential. Color fundus photographs play a crucial role in the grading of DR. With the advancement of artificial intelligence technologies, numerous researchers have conducted studies on DR grading based on deep features and radiomic features extracted from color fundus photographs.</p><p><strong>Method: </strong>We combine deep features and radiomic features to design a feature fusion algorithm. First, we utilize convolutional neural networks to extract deep features from color fundus photographs and employ radiomic methodologies to extract radiomic features. Subsequently, we design a label relaxation-based collaborative learning algorithm for feature fusion.</p><p><strong>Results: </strong>We validate the effectiveness of the proposed method on two fundus image datasets: the DR1 Dataset and the MESSIDOR Dataset. The proposed method achieved 96.86 of AUC on DR1 and 96.34 of AUC on MESSIDOR, which are better than state-of-the-art methods. Also, the divergence between the training AUC and testing AUC increases substantially after the removal of manifold regularization.</p><p><strong>Conclusion: </strong>Label relaxation can enhance the distinguishability of training samples in the label space, thereby improving the model's classification accuracy. Additionally, graph constraints based on manifold learning methods can mitigate overfitting caused by label relaxation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1513971"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028475","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":"Exosomes: new targets for understanding axon guidance in the developing central nervous system.","authors":"Mingyu Liu, Teng Teng","doi":"10.3389/fcell.2024.1510862","DOIUrl":"10.3389/fcell.2024.1510862","url":null,"abstract":"<p><p>Axon guidance is a key event in neural circuit development that drives the correct targeting of axons to their targets through long distances and unique patterns. Exosomes, extracellular vesicles that are smaller than 100 nm, are secreted by most cell types in the brain. Regulation of cell-cell communication, neuroregeneration, and synapse formation by exosomes have been extensively studied. However, the interaction between exosomes and axon guidance molecules is poorly understood. This review summarizes the relationship between exosomes and canonical and non-canonical guidance cues and hypothesizes a possible model for exosomes mediating axon guidance between cells. The roles of exosomes in axon outgrowth, regeneration, and neurodevelopmental disorders are also reviewed, to discuss exosome-guidance interactions as potential clinical therapeutic targets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1510862"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028483","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 quagga mussel, <i>Dreissena rostriformis</i>: a novel model for EcoEvoDevo, environmental research, and the applied sciences.","authors":"Andreas Wanninger, Gudrun Schwarze","doi":"10.3389/fcell.2024.1531560","DOIUrl":"10.3389/fcell.2024.1531560","url":null,"abstract":"<p><p>Bivalve mollusks are globally distributed in marine and freshwater habitats. While exhibiting a relatively uniform bodyplan that is characterized by their eponymous bivalved shell that houses the soft-bodied animal, many lineages have acquired unique morphological, physiological, and molecular innovations that account for their high adaptability to the various properties of aquatic environments such as salinity, flow conditions, or substrate composition. This renders them ideal candidates for studies into the evolutionary trajectories that have resulted in their diversity, but also makes them important players for research concerned with climate change-induced warming and acidification of aquatic habitats. Some species, such as the blue and Mediterranean as well as the zebra and quagga mussels, form biodegradable fibers, the byssus threads. These have significant potential for biomimetic approaches by aiding in developing sustainable textiles and other fiber-based fabrics. Despite this broad span of scientific relevance, bivalves remain dramatically understudied and key resources such as high-quality genomes and developmental transcriptomes in combination with established laboratory protocols to carry out state-of-the-art molecular and morphological studies are only available for less than a handful of species. Here, we report on one of the best-investigated bivalves in this respect, the quagga mussel, <i>Dreissena rostriformis</i>, an invasive freshwater species. We summarize the current state of knowledge and available resources that make the quagga mussel highly amenable for studying adaptive mechanisms for life in hypoosmotic environments, biomineralization, biomimetics, and evolutionary developmental biology. We argue that the unique combination of biological features and the broad relevance of the quagga mussel for the basic and the applied sciences as well as for biomonitoring and conservation biology measures call for intensified research efforts using <i>Dreissena rostriformis</i> as a model.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1531560"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028525","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}