Frontiers in Cell and Developmental Biology最新文献

{"title":"Editorial: Advances in morphogenesis and patterning: zebrafish as a model organism","authors":"Maria Iribarne","doi":"10.3389/fcell.2024.1376663","DOIUrl":"https://doi.org/10.3389/fcell.2024.1376663","url":null,"abstract":"","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"38 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139868669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Advances in morphogenesis and patterning: zebrafish as a model organism","authors":"Maria Iribarne","doi":"10.3389/fcell.2024.1376663","DOIUrl":"https://doi.org/10.3389/fcell.2024.1376663","url":null,"abstract":"","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"64 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139808814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning identifies exosome features related to hepatocellular carcinoma.","authors":"Kai Zhu,&nbsp;Qiqi Tao,&nbsp;Jiatao Yan,&nbsp;Zhichao Lang,&nbsp;Xinmiao Li,&nbsp;Yifei Li,&nbsp;Congcong Fan,&nbsp;Zhengping Yu","doi":"10.3389/fcell.2022.1020415","DOIUrl":"https://doi.org/10.3389/fcell.2022.1020415","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. There is still a lack of effective biomarkers to predict its prognosis. Exosomes participate in intercellular communication and play an important role in the development and progression of cancers. <b>Methods:</b> In this study, two machine learning methods (univariate feature selection and random forest (RF) algorithm) were used to select 13 exosome-related genes (ERGs) and construct an ERG signature. Based on the ERG signature score and ERG signature-related pathway score, a novel RF signature was generated. The expression of BSG and SFN, members of 13 ERGs, was examined using real-time quantitative polymerase chain reaction and immunohistochemistry. Finally, the effects of the inhibition of BSG and SFN on cell proliferation were examined using the cell counting kit-8 (CCK-8) assays. <b>Results:</b> The ERG signature had a good predictive performance, and the ERG score was determined as an independent predictor of HCC overall survival. Our RF signature showed an excellent prognostic ability with the area under the curve (AUC) of 0.845 at 1 year, 0.811 at 2 years, and 0.801 at 3 years in TCGA, which was better than the ERG signature. Notably, the RF signature had a good performance in the prediction of HCC prognosis in patients with the high exosome score and high NK score. Enhanced BSG and SFN levels were found in HCC tissues compared with adjacent normal tissues. The inhibition of BSG and SFN suppressed cell proliferation in Huh7 cells. <b>Conclusion:</b> The RF signature can accurately predict prognosis of HCC patients and has potential clinical value.</p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"1020415"},"PeriodicalIF":5.5,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33490138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Instability of Mutation-Derived Gene Prognostic Signatures for Hepatocellular Carcinoma.","authors":"Ze-Bing Song,&nbsp;Yang Yu,&nbsp;Guo-Pei Zhang,&nbsp;Shao-Qiang Li","doi":"10.3389/fcell.2021.728574","DOIUrl":"https://doi.org/10.3389/fcell.2021.728574","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the major cancer-related deaths worldwide. Genomic instability is correlated with the prognosis of cancers. A biomarker associated with genomic instability might be effective to predict the prognosis of HCC. In the present study, data of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were used. A total of 370 HCC patients from the TCGA database were randomly classified into a training set and a test set. A prognostic signature of the training set based on nine overall survival (OS)-related genomic instability-derived genes (SLCO2A1, RPS6KA2, EPHB6, SLC2A5, PDZD4, CST2, MARVELD1, MAGEA6, and SEMA6A) was constructed, which was validated in the test and TCGA and ICGC sets. This prognostic signature showed more accurate prediction for prognosis of HCC compared with tumor grade, pathological stage, and four published signatures. Cox multivariate analysis revealed that the risk score could be an independent prognostic factor of HCC. A nomogram that combines pathological stage and risk score performed well compared with an ideal model. Ultimately, paired differential expression profiles of genes in the prognostic signature were validated at mRNA and protein level using HCC and paratumor tissues obtained from our institute. Taken together, we constructed and validated a genomic instability-derived gene prognostic signature, which can help to predict the OS of HCC and help us to explore the potential therapeutic targets of HCC.</p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"728574"},"PeriodicalIF":5.5,"publicationDate":"2021-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39539391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Transfer and Regulators of Mesenchymal Stromal Cell Function and Therapeutic Efficacy.","authors":"Amina Mohammadalipour,&nbsp;Sandeep P Dumbali,&nbsp;Pamela L Wenzel","doi":"10.3389/fcell.2020.603292","DOIUrl":"https://doi.org/10.3389/fcell.2020.603292","url":null,"abstract":"<p><p>Mesenchymal stromal cell (MSC) metabolism plays a crucial role in the surrounding microenvironment in both normal physiology and pathological conditions. While MSCs predominantly utilize glycolysis in their native hypoxic niche within the bone marrow, new evidence reveals the importance of upregulation in mitochondrial activity in MSC function and differentiation. Mitochondria and mitochondrial regulators such as sirtuins play key roles in MSC homeostasis and differentiation into mature lineages of the bone and hematopoietic niche, including osteoblasts and adipocytes. The metabolic state of MSCs represents a fine balance between the intrinsic needs of the cellular state and constraints imposed by extrinsic conditions. In the context of injury and inflammation, MSCs respond to reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), such as damaged mitochondria and mitochondrial products, by donation of their mitochondria to injured cells. Through intercellular mitochondria trafficking, modulation of ROS, and modification of nutrient utilization, endogenous MSCs and MSC therapies are believed to exert protective effects by regulation of cellular metabolism in injured tissues. Similarly, these same mechanisms can be hijacked in malignancy whereby transfer of mitochondria and/or mitochondrial DNA (mtDNA) to cancer cells increases mitochondrial content and enhances oxidative phosphorylation (OXPHOS) to favor proliferation and invasion. The role of MSCs in tumor initiation, growth, and resistance to treatment is debated, but their ability to modify cancer cell metabolism and the metabolic environment suggests that MSCs are centrally poised to alter malignancy. In this review, we describe emerging evidence for adaptations in MSC bioenergetics that orchestrate developmental fate decisions and contribute to cancer progression. We discuss evidence and potential strategies for therapeutic targeting of MSC mitochondria in regenerative medicine and tissue repair. Lastly, we highlight recent progress in understanding the contribution of MSCs to metabolic reprogramming of malignancies and how these alterations can promote immunosuppression and chemoresistance. Better understanding the role of metabolic reprogramming by MSCs in tissue repair and cancer progression promises to broaden treatment options in regenerative medicine and clinical oncology.</p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"603292"},"PeriodicalIF":5.5,"publicationDate":"2020-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3389/fcell.2020.603292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38752944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Control of Radial Glia Proliferation and Scaffolding During Cortical Development and Pathology.","authors":"Julien Ferent,&nbsp;Donia Zaidi,&nbsp;Fiona Francis","doi":"10.3389/fcell.2020.578341","DOIUrl":"https://doi.org/10.3389/fcell.2020.578341","url":null,"abstract":"<p><p>During the development of the cortex, newly generated neurons migrate long-distances in the expanding tissue to reach their final positions. Pyramidal neurons are produced from dorsal progenitors, e.g., radial glia (RGs) in the ventricular zone, and then migrate along RG processes basally toward the cortex. These neurons are hence dependent upon RG extensions to support their migration from apical to basal regions. Several studies have investigated how intracellular determinants are required for RG polarity and subsequent formation and maintenance of their processes. Fewer studies have identified the influence of the extracellular environment on this architecture. This review will focus on extracellular factors which influence RG morphology and pyramidal neuronal migration during normal development and their perturbations in pathology. During cortical development, RGs are present in different strategic positions: apical RGs (aRGs) have their cell bodies located in the ventricular zone with an apical process contacting the ventricle, while they also have a basal process extending radially to reach the pial surface of the cortex. This particular conformation allows aRGs to be exposed to long range and short range signaling cues, whereas basal RGs (bRGs, also known as outer RGs, oRGs) have their cell bodies located throughout the cortical wall, limiting their access to ventricular factors. Long range signals impacting aRGs include secreted molecules present in the embryonic cerebrospinal fluid (e.g., Neuregulin, EGF, FGF, Wnt, BMP). Secreted molecules also contribute to the extracellular matrix (fibronectin, laminin, reelin). Classical short range factors include cell to cell signaling, adhesion molecules and mechano-transduction mechanisms (e.g., TAG1, Notch, cadherins, mechanical tension). Changes in one or several of these components influencing the RG extracellular environment can disrupt the development or maintenance of RG architecture on which neuronal migration relies, leading to a range of cortical malformations. First, we will detail the known long range signaling cues impacting RG. Then, we will review how short range cell contacts are also important to instruct the RG framework. Understanding how RG processes are structured by their environment to maintain and support radial migration is a critical part of the investigation of neurodevelopmental disorders.</p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"578341"},"PeriodicalIF":5.5,"publicationDate":"2020-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3389/fcell.2020.578341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38697635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRLF1 Is a Key Regulator in the Ligamentum Flavum Hypertrophy.","authors":"Zhenyu Zheng,&nbsp;Xiang Ao,&nbsp;Peng Li,&nbsp;Zhengnan Lian,&nbsp;Tao Jiang,&nbsp;Zhongmin Zhang,&nbsp;Liang Wang","doi":"10.3389/fcell.2020.00858","DOIUrl":"https://doi.org/10.3389/fcell.2020.00858","url":null,"abstract":"<p><p>Hypertrophy of the ligamentum flavum (HLF) is one of the common causes of lumbar spinal stenosis (LSS). The key molecules and mechanisms responsible for HLF remain unclear. Here, we used an integrated transcriptome and proteomics analysis of human ligamentum flavum (LF), and subsequent immunohistochemistry and real-time PCR assays, to show upregulation of CRLF1 to be the dominant response to HLF. TGF-β1 significantly increased mRNA expression of CRLF1 through SMAD3 pathway. CRLF1 enhanced LF fibrosis via ERK signaling pathway at the post-transcriptional level and was required for the pro-fibrotic effect of TGF-β1. Knockdown of CRLF1 was shown here to reduce fibrosis caused by inflammatory cytokines and mechanical stress. Furthermore, we found that bipedal standing posture can cause HLF and upregulation of CRLF1 expression in mice LF. Overexpression of CRLF1 was indicated to cause HLF <i>in vivo</i>, whereas CRLF1 knockdown impeded the formation of HLF in bipedal standing mice. These results revealed a crucial role of CRLF1 in LF hypertrophy. We propose that inhibition of CRLF1 is a potential therapeutic strategy to treat HLF.</p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"858"},"PeriodicalIF":5.5,"publicationDate":"2020-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3389/fcell.2020.00858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38503234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age and the means of bypassing stasis influence the intrinsic subtype of immortalized human mammary epithelial cells.","authors":"Jonathan K Lee,&nbsp;James C Garbe,&nbsp;Lukas Vrba,&nbsp;Masaru Miyano,&nbsp;Bernard W Futscher,&nbsp;Martha R Stampfer,&nbsp;Mark A LaBarge","doi":"10.3389/fcell.2015.00013","DOIUrl":"https://doi.org/10.3389/fcell.2015.00013","url":null,"abstract":"<p><p>Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence) and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16(INK4A), or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis independently influence the subtype of immortalized human mammary epithelial cells. </p>","PeriodicalId":502752,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":" ","pages":"13"},"PeriodicalIF":5.5,"publicationDate":"2015-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3389/fcell.2015.00013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33165638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}