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Structural Biology of Telomerase and Associated Factors. 端粒酶及其相关因子的结构生物学研究。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-15 DOI: 10.1101/cshperspect.a041697
Zala Sekne, Patryk Ludzia, Sebastian Balch, Thi Hoang Duong Nguyen
{"title":"Structural Biology of Telomerase and Associated Factors.","authors":"Zala Sekne, Patryk Ludzia, Sebastian Balch, Thi Hoang Duong Nguyen","doi":"10.1101/cshperspect.a041697","DOIUrl":"https://doi.org/10.1101/cshperspect.a041697","url":null,"abstract":"<p><p>Telomerase ribonucleoprotein (RNP) plays a crucial role in maintaining telomere length by processively adding telomeric repeats to the 3' ends of chromosomes. Telomerase activation is linked to cancer, while mutations that compromise telomerase function result in diseases such as dyskeratosis congenita. The synthesis of telomeric repeats necessitates two core telomerase components: telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, cellular telomerase holoenzymes encompass a diverse range of protein factors, both constitutively and transiently interacting. These factors are integral to telomerase assembly or regulation at telomeres. This review emphasizes recent advancements in structural studies of telomerase holoenzymes and their associated factors from <i>Tetrahymena thermophila</i>, <i>Saccharomyces cerevisiae</i>, <i>Schizosaccharomyces pombe</i>, and humans. These studies have significantly deepened our molecular understanding not only of the mechanism underlying telomeric repeat synthesis but also of the biological roles of telomerase-associated proteins.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Modeling and Simulating Single and Collective Cell Motility. 单个和集体细胞运动的建模和模拟。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-15 DOI: 10.1101/cshperspect.a041796
Jupiter Algorta, Ali Fele-Paranj, Jack M Hughes, Leah Edelstein-Keshet
{"title":"Modeling and Simulating Single and Collective Cell Motility.","authors":"Jupiter Algorta, Ali Fele-Paranj, Jack M Hughes, Leah Edelstein-Keshet","doi":"10.1101/cshperspect.a041796","DOIUrl":"https://doi.org/10.1101/cshperspect.a041796","url":null,"abstract":"<p><p>We survey a combination of classical and recent experimental and modeling developments in eukaryotic cell migration, from the subcellular processes and regulation, to single and collective cell dynamics. We showcase several examples that demonstrate simulations at several hierarchies: subcellular actin waves, corresponding migratory cell behavior, and collective behavior of several multicellular systems. We argue that the use of shared open-source software packages (such as Morpheus, in our case) to simulate multiscale models would be a boon to the community, allowing us to recreate, investigate, and build on existing work. A brief summary of currently available software is provided.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Bringing Chandelier Cells Out of the Shadows: Exploring the Development of a Unique Neuron Type in the Brain. 将吊灯细胞带出阴影：探索大脑中独特神经元类型的发展。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-15 DOI: 10.1101/cshperspect.a041506
Clara Lenherr, Guilherme Neves, Marcio Guiomar de Oliveira, Juan Burrone
{"title":"Bringing Chandelier Cells Out of the Shadows: Exploring the Development of a Unique Neuron Type in the Brain.","authors":"Clara Lenherr, Guilherme Neves, Marcio Guiomar de Oliveira, Juan Burrone","doi":"10.1101/cshperspect.a041506","DOIUrl":"https://doi.org/10.1101/cshperspect.a041506","url":null,"abstract":"<p><p>Chandelier cells (ChCs) represent a unique GABAergic interneuron in the cortex, yet our knowledge of this sparsely populated cell type has remained equally sparse for many years. New tools, however, have brought ChCs out of the shadows, shedding light on their development and function in the rodent brain and, gradually, gaining insights into their properties in primates. This review will focus on the developmental mechanisms that define ChCs as a unique cell type and, where possible, draw parallels to studies in primates, particularly to work in human tissue. What emerges is a picture of a highly plastic neuron with a unique developmental trajectory that appears to be genetically and functionally conserved in the primate brain.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Biogenesis and Regulation of Telomerase during Development and Cancer. 端粒酶在发育和癌症中的生物发生和调控。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-10 DOI: 10.1101/cshperspect.a041692
Lu Chen, Luis Francisco Zirnberger Batista
{"title":"Biogenesis and Regulation of Telomerase during Development and Cancer.","authors":"Lu Chen, Luis Francisco Zirnberger Batista","doi":"10.1101/cshperspect.a041692","DOIUrl":"10.1101/cshperspect.a041692","url":null,"abstract":"<p><p>Telomerase is a large ribonucleoprotein complex responsible for the addition of telomeric DNA repeats to chromosomal ends. Telomerase is composed of core and accessory components that work in coordination to ensure telomere length is maintained during development and in specific cell types. Telomerase activity is tightly regulated and is strongly increased in most tumor cells. On the other hand, loss-of-function mutations either in accessory factors or in core components of the complex impact telomere maintenance and cause a large spectrum of severe phenotypes, typically described as telomere biology disorders. A central element for efficient telomerase function is the proper biogenesis and assembly of the holoenzyme. Here, we discuss our current understanding of these processes and how they modulate telomerase efficiency. We consider how these processes are influenced by the specific subcellular localization of different telomerase components during different stages of the assembly of the holoenzyme. We describe the tremendous progress made in this area over the last decade and how recently discovered aspects of telomerase biogenesis can be exploited clinically, to actively benefit patients suffering from telomere biology disorders.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981490","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}
引用次数: 0
Shedding Light on Telomere Replication, Insights from the Fission Yeast Schizosaccharomyces pombe. 分裂酵母对端粒复制的启示。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-10 DOI: 10.1101/cshperspect.a041704
Stéphane Coulon
{"title":"Shedding Light on Telomere Replication, Insights from the Fission Yeast <i>Schizosaccharomyces pombe</i>.","authors":"Stéphane Coulon","doi":"10.1101/cshperspect.a041704","DOIUrl":"https://doi.org/10.1101/cshperspect.a041704","url":null,"abstract":"<p><p>Over the years, the fission yeast has become a reference model for telomere biology studies as this organism shares with mammals a highly conserved telomere composition. Here, we highlight the latest discoveries in telomere replication in fission yeast and show how this research brings new insights into the understanding of the replication and maintenance of mammalian telomeres.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Therapeutic Opportunities for Alternative Lengthening of Telomeres (ALT) Cancers. 端粒选择性延长（ALT）癌的治疗机会
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-10 DOI: 10.1101/cshperspect.a041691
Jixuan Gao, Hilda A Pickett
{"title":"Therapeutic Opportunities for Alternative Lengthening of Telomeres (ALT) Cancers.","authors":"Jixuan Gao, Hilda A Pickett","doi":"10.1101/cshperspect.a041691","DOIUrl":"https://doi.org/10.1101/cshperspect.a041691","url":null,"abstract":"<p><p>Cancers that rely on activation of the alternative lengthening of telomeres (ALT) pathway predominantly affect children and adolescents, and are associated with catastrophic outcomes due to a lack of clinically effective, targeted therapeutics. The exponential rise in our understanding of the ALT mechanism in recent years has led to the identification of many therapeutic targets and strategies for patients suffering from these cancers. These include targeting replication fork remodelers and DNA damage response pathways to exacerbate telomere-specific replication stress, inhibiting ALT-mediated telomere synthesis to induce telomere dysfunction, and using oncolytic viruses to selectively kill ALT cancer cells. Herein we will evaluate the advantages and shortfalls of these therapeutic strategies, and discuss current diagnostic opportunities that are a necessary accompaniment to direct ALT therapeutics to patients.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Telomere Dynamics in Zebrafish Aging and Disease. 斑马鱼衰老和疾病的端粒动力学。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041696
Miguel Godinho Ferreira
{"title":"Telomere Dynamics in Zebrafish Aging and Disease.","authors":"Miguel Godinho Ferreira","doi":"10.1101/cshperspect.a041696","DOIUrl":"10.1101/cshperspect.a041696","url":null,"abstract":"<p><p>Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853181","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}
引用次数: 0
Rediscovering and Unrediscovering Gregor Mendel: His Life, Times, and Intellectual Context. 重新发现和重新发现格里高尔-孟德尔：他的生平、时代和思想背景》（Rediscovering and Unrediscovering Gregor Mendel: His Life, Times, and Intellectual Context.
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041812
Sander Gliboff
{"title":"Rediscovering and Unrediscovering Gregor Mendel: His Life, Times, and Intellectual Context.","authors":"Sander Gliboff","doi":"10.1101/cshperspect.a041812","DOIUrl":"10.1101/cshperspect.a041812","url":null,"abstract":"<p><p>Two things about Mendel were \"rediscovered\" in 1900: His famous paper of 1865 and the story of his life and long neglect. Unlike the paper, which anyone could read in its entirety, the story came out only gradually, and many of its elements were misconstrued by Western European scientists. They pictured him as a pure scientist like themselves and were puzzled by or disinterested in his career as a clergyman, his intellectual community in far-off Moravia, and the importance to him of practical plant breeding. This paper recapitulates the process of mythmaking that followed the rediscovery, then shows how more recent historical research has been able to undo it and, in a sense, \"unrediscover\" Mendel.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582604","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}
引用次数: 0
Enteric Glia. 肠胶质细胞
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041368
Meenakshi Rao, Brian D Gulbransen
{"title":"Enteric Glia.","authors":"Meenakshi Rao, Brian D Gulbransen","doi":"10.1101/cshperspect.a041368","DOIUrl":"10.1101/cshperspect.a041368","url":null,"abstract":"<p><p>Enteric glia are a unique type of peripheral neuroglia that accompany neurons in the enteric nervous system (ENS) of the digestive tract. The ENS displays integrative neural circuits that are capable of governing moment-to-moment gut functions independent of input from the central nervous system. Enteric glia are interspersed with neurons throughout these intrinsic gut neural circuits and are thought to fulfill complex roles directed at maintaining homeostasis in the neuronal microenvironment and at neuroeffector junctions in the gut. Changes to glial functions contribute to a wide range of gastrointestinal diseases, but the precise roles of enteric glia in gut physiology and pathophysiology are still under examination. This review summarizes current concepts regarding enteric glial development, diversity, and functions in health and disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476123","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}
引用次数: 0
Physical Forces in Regeneration of Cells and Tissues. 细胞和组织再生中的物理力
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041527
Sindy K Y Tang, Wallace F Marshall
{"title":"Physical Forces in Regeneration of Cells and Tissues.","authors":"Sindy K Y Tang, Wallace F Marshall","doi":"10.1101/cshperspect.a041527","DOIUrl":"10.1101/cshperspect.a041527","url":null,"abstract":"<p><p>The ability to regenerate after the loss of a part is a hallmark of living systems and occurs at both the tissue and organ scales, but also within individual cells. Regeneration entails many processes that are physical and mechanical in nature, including the closure of wounds, the repositioning of material from one place to another, and the restoration of symmetry following perturbations. However, we currently know far more about the genetics and molecular signaling pathways involved in regeneration, and there is a need to investigate the role of physical forces in the process. Here, we will provide an overview of how physical forces may play a role in wound healing and regeneration, in which we compare and contrast regenerative processes at the tissue and cell scales.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161417","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}
引用次数: 0
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