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Epigenetics Beyond the Cell: Supracellular Organization of Fate and Form in Morphogenesis. 超越细胞的表观遗传学：形态发生中命运与形态的超细胞组织。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041497
Rubens Sautchuk, Sichen Yang, Amy Shyer, Alan Rodrigues
{"title":"Epigenetics Beyond the Cell: Supracellular Organization of Fate and Form in Morphogenesis.","authors":"Rubens Sautchuk, Sichen Yang, Amy Shyer, Alan Rodrigues","doi":"10.1101/cshperspect.a041497","DOIUrl":"https://doi.org/10.1101/cshperspect.a041497","url":null,"abstract":"<p><p>How biological systems obtain their shape and structure is a fundamental question with many practical implications. Like much of biology, over the last several decades, tissue and organ morphogenesis has focused on uncovering regulatory mechanisms at the cellular and subcellular scales. Such studies have either implicitly or explicitly reified the view that the creation of form is instructed or controlled by a combination of genetic and molecular processes. However, pioneering early twentieth century biological theorists such as Conrad Waddington cautioned against the total subsummation of biology by, for instance, biochemistry and molecular biology. Through the coining of terms such as \"epigenotype,\" it was argued that processes at every scale between genotype and phenotype were necessary to organize morphogenesis. Thus, organizing processes exist that are not reducible merely to the sum of inputs from \"genes\" and \"environment.\" Here, we argue that uncovering generative epigenetic processes beyond the cell yet within the organism requires a holistically oriented use of physical concepts involving mechanics and material phases. To uncover and clearly articulate such \"supracellular\" processes, we discuss how relations between mesenchymal cells and extracellular matrix (ECM) serve as a powerful model system. Based on the study of mesenchymal-ECM systems, we suggest that it may not be possible to understand the ultimate functional role of gene products such as signaling molecules without an appreciation of supracellular processes in their own right.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977888","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
Backbone Conditional Protein Sequence Design. 主干条件蛋白序列设计。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041517
Justas Dauparas
{"title":"Backbone Conditional Protein Sequence Design.","authors":"Justas Dauparas","doi":"10.1101/cshperspect.a041517","DOIUrl":"https://doi.org/10.1101/cshperspect.a041517","url":null,"abstract":"<p><p>A protein is defined by its amino acid sequence. This sequence and environmental factors shape a protein's 3D structural landscape, which is crucial for the protein's function and activity. Protein design aims to develop novel protein sequences or modify existing ones to perform specific functions or have desired protein properties. The protein sequence space is exponentially large, making protein sequence design a tough problem. This problem can be simplified by considering a backbone conditional protein sequence design that factorizes the design problem into two parts: protein backbone design and backbone-dependent sequence design. This allows for a more efficient search over the sequence space for desired structural features. In this review, we discuss when backbone conditional sequence design is possible and how to assess the performance of different design methods, training data, symmetric design, and the combination of unconditional and conditional sequence models.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989088","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
Life and Death without Telomerase: The Saccharomyces cerevisiae Model. 没有端粒酶的生与死：酿酒酵母模型。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041699
Veronica Martinez-Fernandez, Aurélia Barascu, Maria Teresa Teixeira
{"title":"Life and Death without Telomerase: The <i>Saccharomyces cerevisiae</i> Model.","authors":"Veronica Martinez-Fernandez, Aurélia Barascu, Maria Teresa Teixeira","doi":"10.1101/cshperspect.a041699","DOIUrl":"10.1101/cshperspect.a041699","url":null,"abstract":"<p><p><i>Saccharomyces cerevisiae</i>, a model organism in telomere biology, has been instrumental in pioneering a comprehensive understanding of the molecular processes that occur in the absence of telomerase across eukaryotes. This exploration spans investigations into telomere dynamics, intracellular signaling cascades, and organelle-mediated responses, elucidating their impact on proliferative capacity, genome stability, and cellular variability. Through the lens of budding yeast, numerous sources of cellular heterogeneity have been identified, dissected, and modeled, shedding light on the risks associated with telomeric state transitions, including the evasion of senescence. Moreover, the unraveling of the intricate interplay between the nucleus and other organelles upon telomerase inactivation has provided insights into eukaryotic evolution and cellular communication networks. These contributions, akin to milestones achieved using budding yeast, such as the discovery of the cell cycle, DNA damage checkpoint mechanisms, and DNA replication and repair processes, have been of paramount significance for the telomere field. Particularly, these insights extend to understanding replicative senescence as an anticancer mechanism in humans and enhancing our understanding of eukaryotes' evolution.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853173","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
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 6.9 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":"https://doi.org/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":6.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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
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