Frontiers in Cell and Developmental Biology最新文献

{"title":"Vitamin E supplementation prevents obesogenic diet-induced developmental abnormalities in SR-B1 deficient embryos.","authors":"Alonso Quiroz, Gabriela Belledonne, Fujiko Saavedra, Javier González, Dolores Busso","doi":"10.3389/fcell.2024.1460697","DOIUrl":"https://doi.org/10.3389/fcell.2024.1460697","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic and environmental factors influence the risk of neural tube defects (NTD), congenital malformations characterized by abnormal brain and spine formation. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1), which is involved in the bidirectional transfer of lipids between lipoproteins and cells, exhibit a high prevalence of exencephaly, preventable by maternal vitamin E supplementation. SR-B1 knock-out (KO) embryos are severely deficient in vitamin E and show elevated reactive oxygen species levels during neurulation.</p><p><strong>Methods: </strong>We fed SR-B1 heterozygous female mice a high-fat/high-sugar (HFHS) diet and evaluated the vitamin E and oxidative status in dams and embryos from heterozygous intercrosses. We also determined the incidence of NTD.</p><p><strong>Results and discussion: </strong>HFHS-fed SR-B1 HET females exhibited altered glucose metabolism and excess circulating lipids, along with a higher incidence of embryos with developmental delay and NTD. Vitamin E supplementation partially mitigated HFHS-induced maternal metabolic abnormalities and completely prevented embryonic malformations, likely through indirect mechanisms involving the reduction of oxidative stress and improved lipid handling by the parietal yolk sac.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1460697"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498098","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":"Asymmetric dimethylarginine induces maladaptive function of the blood-brain barrier.","authors":"Tetyana P Buzhdygan, Servio H Ramirez, Miroslav N Nenov","doi":"10.3389/fcell.2024.1476386","DOIUrl":"https://doi.org/10.3389/fcell.2024.1476386","url":null,"abstract":"<p><p>Growing body of evidence suggests that cardiovascular risk factor, asymmetric dimethylarginine (ADMA), can be implicated in the pathogenesis of neurodegenerative and psychiatric disorders. In part, ADMA can affect brain health negatively modulating critical functions of the blood-brain barrier (BBB). The precise mechanisms and consequences of ADMA action on the cerebral vasculature remains unexplored. Here, we evaluated ADMA-induced maladaptation of BBB functions by analyzing real time electrical cell-substrate impedance, paracellular permeability, immune-endothelial interactions, and inflammatory cytokines production by primary human brain microvascular endothelial cells (hBMVEC) treated with ADMA. We found that ADMA disrupted physical barrier function as evident by significant decrease in electrical resistance and increase in paracellular permeability of hBMVEC monolayers. Next, ADMA triggered immune-endothelial interactions since adhesion of primary human monocytes and their extravasation across the endothelial monolayer both were significantly elevated upon treatment with ADMA. Increased levels of cell adhesion molecules (VCAM-1 and RANTES), VEGF-A and inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10, IL-4, IL-2, IL-13, IL-12p70) characterize ADMA-induced hBMVEC dysfunction as inflammatory. Overall, our data suggest that ADMA can impair BBB functions disrupting the endothelial barrier and eliciting neuroinflammatory and neuroimmune responses.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1476386"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498073","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 transcription elongation factors Spt4 and Spt5 control neural progenitor proliferation and are implicated in neuronal remodeling during <i>Drosophila</i> mushroom body development.","authors":"Lea Barthel, Stefani Pettemeridi, Ali Nebras, Hayley Schnaidt, Karoline Fahland, Lea Vormwald, Thomas Raabe","doi":"10.3389/fcell.2024.1434168","DOIUrl":"https://doi.org/10.3389/fcell.2024.1434168","url":null,"abstract":"<p><p>Spt4 and Spt5 form the DRB sensitivity inducing factor (DSIF) complex that regulates transcription elongation at multiple steps including promotor-proximal pausing, processivity and termination. Although this implicated a general role in transcription, several studies pointed to smaller sets of target genes and indicated a more specific requirement in certain cellular contexts. To unravel common or distinct functions of Spt4 and Spt5 <i>in vivo</i>, we generated knock-out alleles for both genes in <i>Drosophila melanogaster</i>. Using the development of the mushroom bodies as a model, we provided evidence for two common functions of Spt4 and Spt5 during mushroom body development, namely control of cell proliferation of neural progenitor cells and remodeling of axonal projections of certain mushroom body neurons. This latter function is not due to a general requirement of Spt4 and Spt5 for axon pathfinding of mushroom body neurons, but due to distinct effects on the expression of genes controlling remodeling.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1434168"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498097","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 different adult stem cell-derived exosomal non-coding RNAs for the treatment of neurological disorders: a narrative review.","authors":"Lebin Ke, Yingying Cao, Zhiwei Lu, Jamal Hallajzadeh","doi":"10.3389/fcell.2024.1459246","DOIUrl":"https://doi.org/10.3389/fcell.2024.1459246","url":null,"abstract":"<p><p>Neurological disorders are being increasingly recognized as major causes of death and disability around the world. Neurological disorders refer to a broad range of medical conditions that affect the brain and spinal cord. These disorders can have various causes, including genetic factors, infections, trauma, autoimmune reactions, or neurodegenerative processes. Each disorder has its own unique symptoms, progression, and treatment options. Optimal communication between interneurons and neuron-glia cells within the homeostatic microenvironment is of paramount importance. Within this microenvironment, exosomes play a significant role in promoting intercellular communication by transferring a diverse cargo of contents, including proteins, lipids, and non-coding RNAs (ncRNAs). Partially, nervous system homeostasis is preserved by various stem cell-derived exosomal ncRNAs, which include circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). The diversity of these exosomal ncRNAs suggests their potential to influence multiple pathways and cellular processes within the nervous system. Stem cell-derived exosomes and their ncRNA contents have been investigated for potential therapeutic uses in neurological disorders, owing to their demonstrated capabilities in neuroprotection, neuroregeneration, and modulation of disease-related pathways. The ability of stem cell-derived exosomes to cross the blood-brain barrier makes them a promising delivery vehicle for therapeutic ncRNAs. This review aims to summarize the current understanding of different stem cell-derived exosomal ncRNAs and their therapeutic potential and clinical applications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1459246"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498072","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":"Radiation-induced skin reactions: oxidative damage mechanism and antioxidant protection.","authors":"Chuchu Liu, Jinlong Wei, Xuanzhong Wang, Qin Zhao, Jincai Lv, Zining Tan, Ying Xin, Xin Jiang","doi":"10.3389/fcell.2024.1480571","DOIUrl":"https://doi.org/10.3389/fcell.2024.1480571","url":null,"abstract":"<p><p>According to official statistics, cancer remains the main reason of death and over 50% of patients with cancer receive radiotherapy. However, adverse consequences after radiation exposure like radiation-induced skin reactions (RISR) have negative or even fatal impact on patients' quality of life (QoL). In this review we summarize the mechanisms and managements of RISRs, a process that involve a variety of extracellular and intracellular signals, among which oxidative stress (OS) are now commonly believed to be the initial part of the occurrence of all types of RISRs. As for the management of RISRs, traditional treatments have been widely used but without satisfying outcomes while some promising therapeutic strategies related to OS still need further researches. In the context we discuss how OS leads to the happening of RISRs of different types, hoping it can shed some light on the exploration of new countermeasures.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1480571"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498095","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":"IMPC-based screening revealed that <i>ROBO1</i> can regulate osteoporosis by inhibiting osteogenic differentiation.","authors":"Xiangzheng Zhang, Yike Wang, Miao Zheng, Qi Wei, Ruizhi Zhang, Keyu Zhu, Qiaocheng Zhai, Youjia Xu","doi":"10.3389/fcell.2024.1450215","DOIUrl":"https://doi.org/10.3389/fcell.2024.1450215","url":null,"abstract":"<p><strong>Introduction: </strong>The utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges.</p><p><strong>Methods: </strong>We first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene.</p><p><strong>Results: </strong>We identified <i>PPP2R2A</i>, <i>RRBP1</i>, <i>HSPB6</i>, <i>SLC22A15</i>, <i>ADAMTS4</i>, <i>ATP8B1</i>, <i>CTNNB1</i>, <i>ROBO1</i>, and <i>EFR3B</i>, which may contribute to osteoporosis. <i>ROBO1</i> was the most significant regulator of osteogenesis in both human and mouse osteoblast. The inhibitory effect of Robo1 knockdown on osteogenic differentiation may be related to the activation of inflammatory signaling pathways.</p><p><strong>Conclusion: </strong>Our study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. <i>ROBO1</i> is a potential target for osteoporosis intervention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1450215"},"PeriodicalIF":4.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498076","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":"Emerging roles of cancer-associated histone mutations in genomic instabilities.","authors":"Priyanka Yadav, Ronit Jain, Rajesh Kumar Yadav","doi":"10.3389/fcell.2024.1455572","DOIUrl":"https://doi.org/10.3389/fcell.2024.1455572","url":null,"abstract":"<p><p>Epigenetic mechanisms often fuel the quick evolution of cancer cells from normal cells. Mutations or aberrant expressions in the enzymes of DNA methylation, histone post-translational modifications, and chromatin remodellers have been extensively investigated in cancer pathogenesis; however, cancer-associated histone mutants have gained momentum in recent decades. Next-generation sequencing of cancer cells has identified somatic recurrent mutations in all the histones (H3, H4, H2A, H2B, and H1) with different frequencies for various tumour types. Importantly, the well-characterised H3K27M, H3G34R/V, and H3K36M mutations are termed as oncohistone mutants because of their wide roles, from defects in cellular differentiation, transcriptional dysregulation, and perturbed epigenomic profiles to genomic instabilities. Mechanistically, these histone mutants impart their effects on histone modifications and/or on irregular distributions of chromatin complexes. Recent studies have identified the crucial roles of the H3K27M and H3G34R/V mutants in the DNA damage response pathway, but their impacts on chemotherapy and tumour progression remain elusive. In this review, we summarise the recent developments in their functions toward genomic instabilities and tumour progression. Finally, we discuss how such a mechanistic understanding can be harnessed toward the potential treatment of tumours harbouring the H3K27M, H3G34R/V, and H3K36M mutations.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1455572"},"PeriodicalIF":4.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498075","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: Understanding the mesenchymal to epithelial transition: a much needed angle for epithelial mesenchymal plasticity.","authors":"Hani Alotaibi, Ralph Meuwissen, A Emre Sayan","doi":"10.3389/fcell.2024.1497515","DOIUrl":"10.3389/fcell.2024.1497515","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1497515"},"PeriodicalIF":4.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461987","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: Reviews and advances in cutting edge microscopy and imaging techniques in membrane trafficking and organellar dynamics.","authors":"Veronika Huntosova, Marco Andreana, Alexandre A Mironov, Duarte C Barral","doi":"10.3389/fcell.2024.1493620","DOIUrl":"https://doi.org/10.3389/fcell.2024.1493620","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1493620"},"PeriodicalIF":4.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461986","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":"Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling.","authors":"David Sedmera, Veronika Olejnickova, Barbora Sankova, Hana Kolesova, Martin Bartos, Alena Kvasilova, Lauren C Phillips, Simon D Bamforth, Helen M Phillips","doi":"10.3389/fcell.2024.1471751","DOIUrl":"10.3389/fcell.2024.1471751","url":null,"abstract":"<p><p>Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1471751"},"PeriodicalIF":4.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461990","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}