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Temporal and clonal characterization of neural stem cell niche recruitment in the medaka neuromast medaka神经肥大神经干细胞生态位募集的时间和克隆特征
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203837
Jasmin Onistschenko, Sabrina Kaminsky, Javier Vazquez-Marín, Karen Gross, Tianyu Wang , Ali Seleit , Melanie Dörr , Lázaro Centanin
{"title":"Temporal and clonal characterization of neural stem cell niche recruitment in the medaka neuromast","authors":"Jasmin Onistschenko,&nbsp;Sabrina Kaminsky,&nbsp;Javier Vazquez-Marín,&nbsp;Karen Gross,&nbsp;Tianyu Wang ,&nbsp;Ali Seleit ,&nbsp;Melanie Dörr ,&nbsp;Lázaro Centanin","doi":"10.1016/j.cdev.2023.203837","DOIUrl":"10.1016/j.cdev.2023.203837","url":null,"abstract":"<div><p>Stem cell populations are defined by their capacity to self-renew and to generate differentiated progeny. These unique characteristics largely depend on the stem cell micro-environment, the so-called stem cell niche. Niches were identified for most adult stem cells studied so far, but we know surprisingly little about how somatic stem cells and their niche come together during organ formation. Using the neuromasts of teleost fish, we have previously reported that neural stem cells recruit their niche from neighboring epithelial cells, which go through a morphological and molecular transformation. Here, we tackle quantitative, temporal, and clonal aspects of niche formation in neuromasts by using 4D imaging in transgenic lines, and lineage analysis in mosaic fish. We show that niche recruitment happens in a defined temporal window during the formation of neuromasts in medaka, and after that, the niche is enlarged mainly by the proliferation of niche cells. Niche recruitment is a non-clonal process that feeds from diverse epithelial cells that do not display a preferential position along the circumference of the forming neuromast. Additionally, we cover niche formation and expansion in zebrafish to show that distant species show common features during organogenesis in the lateral line system. Overall, our findings shed light on the process of niche formation, fundamental for the maintenance of stem cells not only in medaka but also in many other multicellular organisms.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203837"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep machine learning for cell segmentation and quantitative analysis of radial plant growth 植物径向生长的细胞分割和定量分析的深度机器学习
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203842
Alexandra Zakieva , Lorenzo Cerrone , Thomas Greb
{"title":"Deep machine learning for cell segmentation and quantitative analysis of radial plant growth","authors":"Alexandra Zakieva ,&nbsp;Lorenzo Cerrone ,&nbsp;Thomas Greb","doi":"10.1016/j.cdev.2023.203842","DOIUrl":"10.1016/j.cdev.2023.203842","url":null,"abstract":"<div><p>Plants produce the major part of terrestrial biomass and are long-term deposits of atmospheric carbon. This capacity is to a large extent due to radial growth of woody species – a process driven by cambium stem cells located in distinct niches of shoot and root axes. In the model species <em>Arabidopsis thaliana</em>, thousands of cells are produced by the cambium in radial orientation generating a complex organ anatomy enabling long-distance transport, mechanical support and protection against biotic and abiotic stressors. These complex organ dynamics make a comprehensive and unbiased analysis of radial growth challenging and asks for tools for automated quantification. Here, we combined the recently developed PlantSeg and MorphographX image analysis tools, to characterize tissue morphogenesis of the <em>Arabidopsis</em> hypocotyl. After sequential training of segmentation models on ovules, shoot apical meristems and adult hypocotyls using deep machine learning, followed by the training of cell type classification models, our pipeline segments complex images of transverse hypocotyl sections with high accuracy and classifies central hypocotyl cell types. By applying our pipeline on both wild type and <em>phloem intercalated with xylem</em> (<em>pxy</em>) mutants, we also show that this strategy faithfully detects major anatomical aberrations. Collectively, we conclude that our established pipeline is a powerful phenotyping tool comprehensively extracting cellular parameters and providing access to tissue topology during radial plant growth.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203842"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mathematics of neural stem cells: Linking data and processes 神经干细胞的数学:连接数据和过程
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203849
Diana-Patricia Danciu , Jooa Hooli , Ana Martin-Villalba , Anna Marciniak-Czochra
{"title":"Mathematics of neural stem cells: Linking data and processes","authors":"Diana-Patricia Danciu ,&nbsp;Jooa Hooli ,&nbsp;Ana Martin-Villalba ,&nbsp;Anna Marciniak-Czochra","doi":"10.1016/j.cdev.2023.203849","DOIUrl":"10.1016/j.cdev.2023.203849","url":null,"abstract":"<div><p>Adult stem cells are described as a discrete population of cells that stand at the top of a hierarchy of progressively differentiating cells. Through their unique ability to self-renew and differentiate, they regulate the number of end-differentiated cells that contribute to tissue physiology. The question of how discrete, continuous, or reversible the transitions through these hierarchies are and the precise parameters that determine the ultimate performance of stem cells in adulthood are the subject of intense research. In this review, we explain how mathematical modelling has improved the mechanistic understanding of stem cell dynamics in the adult brain. We also discuss how single-cell sequencing has influenced the understanding of cell states or cell types. Finally, we discuss how the combination of single-cell sequencing technologies and mathematical modelling provides a unique opportunity to answer some burning questions in the field of stem cell biology.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203849"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9898932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Physical biomarkers for human hematopoietic stem and progenitor cells 人造血干细胞和祖细胞的物理生物标志物
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203845
Motomu Tanaka , Judith Thoma , Laura Poisa-Beiro , Patrick Wuchter , Volker Eckstein , Sascha Dietrich , Caroline Pabst , Carsten Müller-Tidow , Takao Ohta , Anthony D. Ho
{"title":"Physical biomarkers for human hematopoietic stem and progenitor cells","authors":"Motomu Tanaka ,&nbsp;Judith Thoma ,&nbsp;Laura Poisa-Beiro ,&nbsp;Patrick Wuchter ,&nbsp;Volker Eckstein ,&nbsp;Sascha Dietrich ,&nbsp;Caroline Pabst ,&nbsp;Carsten Müller-Tidow ,&nbsp;Takao Ohta ,&nbsp;Anthony D. Ho","doi":"10.1016/j.cdev.2023.203845","DOIUrl":"10.1016/j.cdev.2023.203845","url":null,"abstract":"<div><p>Adhesion of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow niche plays critical roles in the maintenance of the most primitive HSPCs. The interactions of HSPC−niche interactions are clinically relevant in acute myeloid leukemia (AML), because (i) leukemia-initiating cells adhered to the marrow niche are protected from the cytotoxic effect by chemotherapy and (ii) mobilization of HSPCs from healthy donors' bone marrow is crucial for the effective stem cell transplantation. However, although many clinical agents have been developed for the HSPC mobilization, the effects caused by the extrinsic molecular cues were traditionally evaluated based on phenomenological observations. This review highlights the recent interdisciplinary challenges of hematologists, biophysicists and cell biologists towards the design of defined <em>in vitro</em> niche models and the development of physical biomarkers for quantitative indexing of differential effects of clinical agents on human HSPCs.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203845"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multimodal Wnt signalling in the mouse neocortex 小鼠新皮层中的多模态Wnt信号
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203838
Fabio Da Silva , Christof Niehrs
{"title":"Multimodal Wnt signalling in the mouse neocortex","authors":"Fabio Da Silva ,&nbsp;Christof Niehrs","doi":"10.1016/j.cdev.2023.203838","DOIUrl":"10.1016/j.cdev.2023.203838","url":null,"abstract":"<div><p>The neocortex is the site of higher cognitive functions and its development is tightly regulated by cell signalling pathways. Wnt signalling is inexorably linked with neocortex development but its precise role remains unclear. Most studies demonstrate that Wnt/β-catenin regulates neural progenitor self-renewal but others suggest it can also promote differentiation. Wnt/STOP signalling is a novel branch of the Wnt pathway that stabilizes proteins during G2/M by inhibiting glycogen synthase kinase 3 (GSK3)-mediated protein degradation. Recent data from our work in <span>Da Silva et al. (2021)</span> demonstrate that Wnt/STOP is involved in neocortex development where, by stabilizing the neurogenic transcription factors Sox4 and Sox11, it promotes neural progenitor differentiation. We also show that Wnt/STOP regulates asymmetric cell division and cell cycle dynamics in apical and basal progenitors, respectively. Our study reveals a division of labour in the Wnt signalling pathway by suggesting that Wnt/STOP is the primary driver of cortical neurogenesis while Wnt/β-catenin is mainly responsible for self-renewal. These results resolve a decades-old question on the role of Wnt signalling in cortical neural progenitors.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203838"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential expression of endothelial protein C receptor (EPCR) in hematopoietic stem and multipotent progenitor cells in young and old mice 内皮蛋白C受体(EPCR)在年轻和年老小鼠造血干细胞和多能祖细胞中的差异表达
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203843
Dawn S. Lin , Andreas Trumpp
{"title":"Differential expression of endothelial protein C receptor (EPCR) in hematopoietic stem and multipotent progenitor cells in young and old mice","authors":"Dawn S. Lin ,&nbsp;Andreas Trumpp","doi":"10.1016/j.cdev.2023.203843","DOIUrl":"10.1016/j.cdev.2023.203843","url":null,"abstract":"<div><p><span><span>Endothelial protein C receptor (EPCR) has emerged as one of the most conserved and reliable surface markers for the prospective identification and isolation of </span>hematopoietic stem cells (HSCs). Prior studies have consistently demonstrated that EPCR expression enriches HSCs capable of long-term multilineage repopulation in both mouse and human across different hematopoietic tissues, including bone marrow (BM), fetal liver and ex vivo HSC expansion cultures. However, little is known about the expression profiles of EPCR in multipotent progenitor (MPP) populations located immediately downstream of HSCs in the hematopoietic hierarchy and which play a major role in sustaining lifelong blood cell production. Here, we incorporate EPCR antibody detection into a multi-parameter flow cytometric panel, which allows accurate identification of HSCs and five MPP subsets (MPP1-5) in mouse BM. Our data reveal that all MPP populations contain EPCR-expressing cells. Multipotent MPP1 and MPP5 contain higher proportion of EPCR</span><sup>+</sup><span> cells compared to the more lineage-biased MPP2–4. Notably, high expression of EPCR enriches phenotypic HSC and MPP5, but not MPP1. Comparison of EPCR expression profiles between young and old BM reveals ageing mediated expansion of EPCR-expressing cells only in HSCs, but not in any of the MPP populations. Collectively, our study provides a comprehensive characterization of the surface expression pattern of EPCR in mouse HSC and MPP1–5 cells during normal and aged hematopoiesis.</span></p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203843"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MiR-29b level-mediated regulation of Klotho methylation via DNMT3A targeting in chronic obstructive pulmonary disease 通过DNMT3A靶向MiR-29b水平介导的慢性阻塞性肺疾病Klotho甲基化调控
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203827
Jie Qiu , Xiuming Liu , Guilan Yang , Zhenzhen Gui , Shengquan Ding
{"title":"MiR-29b level-mediated regulation of Klotho methylation via DNMT3A targeting in chronic obstructive pulmonary disease","authors":"Jie Qiu ,&nbsp;Xiuming Liu ,&nbsp;Guilan Yang ,&nbsp;Zhenzhen Gui ,&nbsp;Shengquan Ding","doi":"10.1016/j.cdev.2023.203827","DOIUrl":"10.1016/j.cdev.2023.203827","url":null,"abstract":"<div><p><span>Chronic obstructive pulmonary disease<span> (COPD) is a chronic lung disease characterized by chronic bronchitis and emphysema. Cigarette smoke extract (CSE) is the predominant cause of COPD. This study aimed to investigate the effects of miR-29b and their underlying mechanisms in a COPD cell model. MiR-29b and DNMT3A expression in lung tissue samples (taken at least 5 cm away from the tumor lesion) of NSCLC cases with smoking (n = 30), without smoking (n = 30), and with COPD (with smoking) (n = 30) was researched by qRT-PCR. A medium containing 10 % CSE was employed to induce murine </span></span>alveolar macrophage<span><span> MH-S cells to establish COPD cells. 5-Aza-cdr (5-AZA-2′-deoxycytidine) was used to block DNMT3A. The relationship and interaction between miR-29b and DNMT3A were validated through the dual luciferase<span><span> reporter assay. The expression levels of macrophage M1 polarization marker proteins iNOS and TNF-α, DNMT3A, and Klotho protein were monitored using </span>western blotting. The </span></span>methylation<span><span> levels of the miR-29b precursor gene and Klotho promoter were detected by quantitative methylation-specific PCR (MS-qPCR). The levels of IL-1β, IL-6, and TNF-α in cell culture medium were detected via ELISA. It was found that the expression of miR-29b was downregulated, as a result of increased </span>DNA methylation, and that of DNMT3A was upregulated in the lung tissues of NSCLC cases with COPD (with smoking). DNMT3A expression was negatively correlated with miR-29b expression in the lung tissues of NSCLC cases with COPD (with smoking). In addition, miR-29b expression was distinctly downregulated in CSE-induced MH-S cells and inhibited CSE-induced M1 polarization and inflammation. Importantly, DNMT3A was identified as a direct target gene of miR-29b. MiR-29b is negatively regulated by DNMT3A-mediated DNA methylation. Moreover, Klotho expression was downregulated and the Klotho promoter methylation level was increased in lung tissues of NSCLC cases with COPD (with smoking). The negative feedback between miR-29b and DNMT3A modulates CSE-induced M1 polarization and inflammation in macrophages as well as Klotho promoter methylation in CSE-mediated MH-S. Collectively, these findings indicate that the miR-29b level in COPD controls Klotho methylation via DNMT3, which maybe a promising target for the treatment of COPD.</span></span></p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203827"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9535536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell RNA sequencing of mouse lower respiratory tract epithelial cells: A meta-analysis 小鼠下呼吸道上皮细胞单细胞RNA测序:荟萃分析
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203847
Leila R. Martins , Hanno Glimm , Claudia Scholl
{"title":"Single-cell RNA sequencing of mouse lower respiratory tract epithelial cells: A meta-analysis","authors":"Leila R. Martins ,&nbsp;Hanno Glimm ,&nbsp;Claudia Scholl","doi":"10.1016/j.cdev.2023.203847","DOIUrl":"10.1016/j.cdev.2023.203847","url":null,"abstract":"<div><p>The respiratory system is a vital component of our body, essential for both oxygen uptake and immune defense. Knowledge of cellular composition and function in different parts of the respiratory tract provides the basis for a better understanding of the pathological processes involved in various diseases such as chronic respiratory diseases and cancer. Single-cell RNA sequencing (scRNA-seq) is a proficient approach for the identification and transcriptional characterization of cellular phenotypes. Although the mouse is an essential tool for the study of lung development, regeneration, and disease, a scRNA-seq mouse atlas of the lung in which all epithelial cell types are included and annotated systematically is lacking. Here, we established a single-cell transcriptome landscape of the mouse lower respiratory tract by performing a meta-analysis of seven different studies in which mouse lungs and trachea were analyzed by droplet and/or plate-based scRNA-seq technologies. We provide information on the best markers for each epithelial cell type, propose surface markers for the isolation of viable cells, harmonized the annotation of cell types, and compare the mouse single-cell transcriptomes with human scRNA-seq data of the lung.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203847"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The surface ectoderm exhibits spatially heterogenous tension that correlates with YAP localisation during spinal neural tube closure in mouse embryos 小鼠胚胎脊髓神经管闭合过程中,外胚层表面表现出空间异质性张力,这与YAP定位有关
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203840
Abigail R. Marshall, Gabriel L. Galea, Andrew J. Copp, Nicholas D.E. Greene
{"title":"The surface ectoderm exhibits spatially heterogenous tension that correlates with YAP localisation during spinal neural tube closure in mouse embryos","authors":"Abigail R. Marshall,&nbsp;Gabriel L. Galea,&nbsp;Andrew J. Copp,&nbsp;Nicholas D.E. Greene","doi":"10.1016/j.cdev.2023.203840","DOIUrl":"10.1016/j.cdev.2023.203840","url":null,"abstract":"<div><p>The single cell layer of surface ectoderm (SE) which overlies the closing neural tube (NT) plays a crucial biomechanical role during mammalian NT closure (NTC), challenging previous assumptions that it is only passive to the force-generating neuroepithelium (NE). Failure of NTC leads to congenital malformations known as NT defects (NTDs), including spina bifida (SB) and anencephaly in the spine and brain respectively. In several mouse NTD models, SB is caused by misexpression of SE-specific genes and is associated with disrupted SE mechanics, including loss of rostrocaudal cell elongation believed to be important for successful closure. In this study, we asked how SE mechanics affect NT morphology, and whether the characteristic rostrocaudal cell elongation at the progressing closure site is a response to tension anisotropy in the SE. We show that blocking SE-specific E-cadherin in <em>ex utero</em> mouse embryo culture influences NT morphology, as well as the F-actin cable. Cell border ablation shows that cell shape is not due to tension anisotropy, but that there are regional differences in SE tension. We also find that YAP nuclear translocation reflects regional tension heterogeneity, and that its expression is sensitive to pharmacological reduction of tension. In conclusion, our results confirm that the SE is a biomechanically important tissue for spinal NT morphogenesis and suggest a possible role of spatial regulation of cellular tension which could regulate downstream gene expression <em>via</em> mechanically-sensitive YAP activity.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203840"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cyclopamine targeting hedgehog modulates nuclear control of the osteoblast activity 靶向hedgehog基因的环巴胺调节成骨细胞活性的核控制
IF 3.9 4区 生物学
Cells and Development Pub Date : 2023-06-01 DOI: 10.1016/j.cdev.2023.203836
Célio J. da Costa Fernandes, Marcel Rodrigues Ferreira, Willian Fernando Zambuzzi
{"title":"Cyclopamine targeting hedgehog modulates nuclear control of the osteoblast activity","authors":"Célio J. da Costa Fernandes,&nbsp;Marcel Rodrigues Ferreira,&nbsp;Willian Fernando Zambuzzi","doi":"10.1016/j.cdev.2023.203836","DOIUrl":"10.1016/j.cdev.2023.203836","url":null,"abstract":"<div><p><span><span>It is known that cellular events underlying the processes of bone maintenance, remodeling, and repair have their basis in the embryonic production of bone. Shh signaling is widely described developing important morphogenetic control in bone by modifying the activity of osteoblast. Furthermore, identifying whether it is associated with the modulation of nuclear control is very important to be the basis for further applications. Experimentally, osteoblasts were exposed with </span>cyclopamine (CICLOP) considering up to 1 day and 7 days, here considered an acute and chronic responses respectively. Firstly, we have validated the osteogenic model in vitro by exposing the osteoblasts to classical differentiating solution up to 7 days to allow the analysis of </span>alkaline phosphatase<span><span> and mineralization<span>. Conversely, our data shows that differentiating osteoblasts present higher activity of inflammasome-related genes, while Shh signaling members were lower, suggesting a negative feedback between them. Thereafter, to better know about the role of Shh signaling on this manner, functional assays using CICLOP (5 μM) were performed and the data validates the previously hypothesis that Shh represses inflammasome related genes activities. Altogether, our data supports the anti-inflammatory effect of Shh signaling by suppressing Tnfα, Tgfβ and inflammasome related genes during osteoblast differentiation, and this comprehension might support the understanding the molecular and cellular mechanisms related in </span></span>bone regeneration by reporting molecular-related osteoblast differentiation.</span></p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"174 ","pages":"Article 203836"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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