Emerging Topics in Life Sciences最新文献_第3页

Stem cell-derived models of spinal neurulation. 源自干细胞的脊髓神经再生模型。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-18 DOI: 10.1042/ETLS20230087

Camil Mirdass, Martin Catala, Mikaëlle Bocel, Stéphane Nedelec, Vanessa Ribes

{"title":"Stem cell-derived models of spinal neurulation.","authors":"Camil Mirdass, Martin Catala, Mikaëlle Bocel, Stéphane Nedelec, Vanessa Ribes","doi":"10.1042/ETLS20230087","DOIUrl":"10.1042/ETLS20230087","url":null,"abstract":"Neurulation is a critical step in early embryonic development, giving rise to the neural tube, the primordium of the central nervous system in amniotes. Understanding this complex, multi-scale, multi-tissue morphogenetic process is essential to provide insights into normal development and the etiology of neural tube defects. Innovations in tissue engineering have fostered the generation of pluripotent stem cell-based in vitro models, including organoids, that are emerging as unique tools for delving into neurulation mechanisms, especially in the context of human development. Each model captures specific aspects of neural tube morphogenesis, from epithelialization to neural tissue elongation, folding and cavitation. In particular, the recent models of human and mouse trunk morphogenesis, such as gastruloids, that form a spinal neural plate-like or neural tube-like structure are opening new avenues to study normal and pathological neurulation. Here, we review the morphogenetic events generating the neural tube in the mammalian embryo and questions that remain unanswered. We discuss the advantages and limitations of existing in vitro models of neurulation and possible future technical developments.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":"7 4","pages":"423-437"},"PeriodicalIF":3.3,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812155","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}

引用次数: 0

Haematopoietic development and HSC formation in vitro: promise and limitations of gastruloid models. 体外造血发育和造血干细胞的形成：胃肠模型的前景和局限性。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-18 DOI: 10.1042/ETLS20230091

Liza Dijkhuis, Ayona Johns, Denise Ragusa, Susanne C van den Brink, Cristina Pina

{"title":"Haematopoietic development and HSC formation in vitro: promise and limitations of gastruloid models.","authors":"Liza Dijkhuis, Ayona Johns, Denise Ragusa, Susanne C van den Brink, Cristina Pina","doi":"10.1042/ETLS20230091","DOIUrl":"10.1042/ETLS20230091","url":null,"abstract":"Haematopoietic stem cells (HSCs) are the most extensively studied adult stem cells. Yet, six decades after their first description, reproducible and translatable generation of HSC in vitro remains an unmet challenge. HSC production in vitro is confounded by the multi-stage nature of blood production during development. Specification of HSC is a late event in embryonic blood production and depends on physical and chemical cues which remain incompletely characterised. The precise molecular composition of the HSC themselves is incompletely understood, limiting approaches to track their origin in situ in the appropriate cellular, chemical and mechanical context. Embryonic material at the point of HSC emergence is limiting, highlighting the need for an in vitro model of embryonic haematopoietic development in which current knowledge gaps can be addressed and exploited to enable HSC production. Gastruloids are pluripotent stem cell-derived 3-dimensional (3D) cellular aggregates which recapitulate developmental events in gastrulation and early organogenesis with spatial and temporal precision. Gastruloids self-organise multi-tissue structures upon minimal and controlled external cues, and are amenable to live imaging, screening, scaling and physicochemical manipulation to understand and translate tissue formation. In this review, we consider the haematopoietic potential of gastruloids and review early strategies to enhance blood progenitor and HSC production. We highlight possible strategies to achieve HSC production from gastruloids, and discuss the potential of gastruloid systems in illuminating current knowledge gaps in HSC specification.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":"7 4","pages":"439-454"},"PeriodicalIF":3.3,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812151","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}

引用次数: 0

Gastruloid optimization. 肠胚优化。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-18 DOI: 10.1042/ETLS20230096

Lara Avni, Naama Farag, Binita Ghosh, Iftach Nachman

引用次数: 0

Gastruloids - a minimalistic model to study complex developmental metabolism. 胃泌素瘤--研究复杂发育代谢的最小模型

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-18 DOI: 10.1042/ETLS20230082

Chaitanya Dingare, Ben Steventon

引用次数: 0

Learning the mechanobiology of development from gastruloids. 从胃体中学习发育的机械生物学。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-18 DOI: 10.1042/ETLS20230081

Pierre-François Lenne, Sham Tlili

引用次数: 0

The molecular mechanisms of spinocerebellar ataxias for DNA repeat expansion in disease. 脊髓小脑性共济失调症的分子机制--DNA重复扩增在疾病中的作用。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230013

Manish Kumar, Nishu Tyagi, Mohammed Faruq

{"title":"The molecular mechanisms of spinocerebellar ataxias for DNA repeat expansion in disease.","authors":"Manish Kumar, Nishu Tyagi, Mohammed Faruq","doi":"10.1042/ETLS20230013","DOIUrl":"10.1042/ETLS20230013","url":null,"abstract":"Spinocerebellar ataxias (SCAs) are a heterogenous group of neurodegenerative disorders which commonly inherited in an autosomal dominant manner. They cause muscle incoordination due to degeneration of the cerebellum and other parts of nervous system. Out of all the characterized (>50) SCAs, 14 SCAs are caused due to microsatellite repeat expansion mutations. Repeat expansions can result in toxic protein gain-of-function, protein loss-of-function, and/or RNA gain-of-function effects. The location and the nature of mutation modulate the underlying disease pathophysiology resulting in varying disease manifestations. Potential toxic effects of these mutations likely affect key major cellular processes such as transcriptional regulation, mitochondrial functioning, ion channel dysfunction and synaptic transmission. Involvement of several common pathways suggests interlinked function of genes implicated in the disease pathogenesis. A better understanding of the shared and distinct molecular pathogenic mechanisms in these diseases is required to develop targeted therapeutic tools and interventions for disease management. The prime focus of this review is to elaborate on how expanded 'CAG' repeats contribute to the common modes of neurotoxicity and their possible therapeutic targets in management of such devastating disorders.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":" ","pages":"289-312"},"PeriodicalIF":3.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527214","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}

引用次数: 0

Advances in the discovery and analyses of human tandem repeats. 人类串联重复序列的发现和分析进展。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230074

Mark J P Chaisson, Arvis Sulovari, Paul N Valdmanis, Danny E Miller, Evan E Eichler

引用次数: 0

Genetic modifiers of repeat expansion disorders. 重复扩增障碍的遗传修饰物。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230015

Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J Hensman Moss, Sarah J Tabrizi

{"title":"Genetic modifiers of repeat expansion disorders.","authors":"Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J Hensman Moss, Sarah J Tabrizi","doi":"10.1042/ETLS20230015","DOIUrl":"10.1042/ETLS20230015","url":null,"abstract":"Repeat expansion disorders (REDs) are monogenic diseases caused by a sequence of repetitive DNA expanding above a pathogenic threshold. A common feature of the REDs is a strong genotype-phenotype correlation in which a major determinant of age at onset (AAO) and disease progression is the length of the inherited repeat tract. Over a disease-gene carrier's life, the length of the repeat can expand in somatic cells, through the process of somatic expansion which is hypothesised to drive disease progression. Despite being monogenic, individual REDs are phenotypically variable, and exploring what genetic modifying factors drive this phenotypic variability has illuminated key pathogenic mechanisms that are common to this group of diseases. Disease phenotypes are affected by the cognate gene in which the expansion is found, the location of the repeat sequence in coding or non-coding regions and by the presence of repeat sequence interruptions. Human genetic data, mouse models and in vitro models have implicated the disease-modifying effect of DNA repair pathways via the mechanisms of somatic mutation of the repeat tract. As such, developing an understanding of these pathways in the context of expanded repeats could lead to future disease-modifying therapies for REDs.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":" ","pages":"325-337"},"PeriodicalIF":3.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683478","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}

引用次数: 0

The role of tandem repeat expansions in brain disorders. 串联重复扩展在脑部疾病中的作用。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230022

Mary Anne Panoyan, Frank R Wendt

引用次数: 0

Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions. 解开神经发育障碍和短串联CGG重复扩增之间的联系。

IF 3.3

Emerging Topics in Life Sciences Pub Date : 2023-12-14 DOI: 10.1042/ETLS20230021

Dale J Annear, R Frank Kooy

{"title":"Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions.","authors":"Dale J Annear, R Frank Kooy","doi":"10.1042/ETLS20230021","DOIUrl":"10.1042/ETLS20230021","url":null,"abstract":"Neurodevelopmental disorders (NDDs) encompass a diverse group of disorders characterised by impaired cognitive abilities and developmental challenges. Short tandem repeats (STRs), repetitive DNA sequences found throughout the human genome, have emerged as potential contributors to NDDs. Specifically, the CGG trinucleotide repeat has been implicated in a wide range of NDDs, including Fragile X Syndrome (FXS), the most common inherited form of intellectual disability and autism. This review focuses on CGG STR expansions associated with NDDs and their impact on gene expression through repeat expansion-mediated epigenetic silencing. We explore the molecular mechanisms underlying CGG-repeat expansion and the resulting epigenetic modifications, such as DNA hypermethylation and gene silencing. Additionally, we discuss the involvement of other CGG STRs in neurodevelopmental diseases. Several examples, including FMR1, AFF2, AFF3, XYLT1, FRA10AC1, CBL, and DIP2B, highlight the complex relationship between CGG STR expansions and NDDs. Furthermore, recent advancements in this field are highlighted, shedding light on potential future research directions. Understanding the role of STRs, particularly CGG-repeats, in NDDs has the potential to uncover novel diagnostic and therapeutic strategies for these challenging disorders.","PeriodicalId":46394,"journal":{"name":"Emerging Topics in Life Sciences","volume":" ","pages":"265-275"},"PeriodicalIF":3.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139581","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}

引用次数: 0