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Regulation of Human Telomerase: from Molecular Interactions to Population Genetics. 人类端粒酶的调控：从分子相互作用到群体遗传学。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041693
Annika Martin, Dirk Hockemeyer
{"title":"Regulation of Human Telomerase: from Molecular Interactions to Population Genetics.","authors":"Annika Martin, Dirk Hockemeyer","doi":"10.1101/cshperspect.a041693","DOIUrl":"https://doi.org/10.1101/cshperspect.a041693","url":null,"abstract":"<p><p>Human telomeres play critical roles in protecting chromosome ends and preserving genomic integrity. Telomerase, essential for maintaining telomere length and cellular replicative capacity, is only expressed in a small subset of human cells: stem and progenitor populations. Conversely, most somatic cells' telomeres shorten with each cell division; this shortening provides a potent tumor suppressor mechanism. Thus, telomerase regulation shapes not only cellular life span and differentiation, but also the regenerative capacity and long-term integrity of tissues. Here, we review the current understanding of telomere length control and telomerase regulation in humans, from molecular interactions at chromosome ends to the tissue-specific variation of telomere length dynamics, drawing insight from pluripotent and adult stem cell populations, as well as telomerase dysregulation in cancer and telomere biology disorders.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101472","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
How Shelterin Orchestrates the Replication and Protection of Telomeres. 庇护蛋白如何协调端粒的复制和保护。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041685
Titia de Lange
{"title":"How Shelterin Orchestrates the Replication and Protection of Telomeres.","authors":"Titia de Lange","doi":"10.1101/cshperspect.a041685","DOIUrl":"https://doi.org/10.1101/cshperspect.a041685","url":null,"abstract":"<p><p>Efforts to determine how telomeres solve the end-protection problem led to the discovery of shelterin, a conserved six-subunit protein complex that specifically binds to the long arrays of telomeric TTAGGG repeats at vertebrate chromosome ends. The mechanisms by which shelterin prevents telomeres from being detected as sites of DNA damage and how shelterin prevents inappropriate DNA repair pathways are now largely known. More recently, shelterin has emerged as a central player in solving the second major problem at telomeres: how to complete the duplication of telomeric DNA. This end-replication problem results from the inability of the canonical DNA replication machinery to maintain the DNA at chromosome ends. Shelterin solves this problem by recruiting two enzymes that can replenish the lost telomeric repeats: telomerase and CST-Polα/primase. How shelterin accomplishes these critical tasks is reviewed here.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101515","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
Modern Modeling of Single-Cell Migration: From Membrane Tension and Galvanotaxis to Machine Learning. 单细胞迁移的现代建模：从膜张力和流原性到机器学习。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041745
Wenzheng Shi, Alex Mogilner
{"title":"Modern Modeling of Single-Cell Migration: From Membrane Tension and Galvanotaxis to Machine Learning.","authors":"Wenzheng Shi, Alex Mogilner","doi":"10.1101/cshperspect.a041745","DOIUrl":"https://doi.org/10.1101/cshperspect.a041745","url":null,"abstract":"<p><p>Cell migration phenomenon has inspired and benefited from computational modeling for decades. Here, we review recent applications of traditional bottom-up modeling to three aspects of cell migration: the role of membrane tension (MT) in organizing directional cell motility, the role of the electric field (EF) as the directional cue for migration, and the mechanics of three-dimensional migration. We then discuss nascent applications of machine learning (ML) to cell migration and galvanotaxis. We focus on the migratory mechanisms of the single cell and highlight the feedback between theory and experiment.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101143","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
Hidden Treasures of the Genetic Systems in Yeast Mitochondria. 酵母线粒体遗传系统的隐藏宝藏。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041849
Jozef Nosek, Ľubomír Tomáška
{"title":"Hidden Treasures of the Genetic Systems in Yeast Mitochondria.","authors":"Jozef Nosek, Ľubomír Tomáška","doi":"10.1101/cshperspect.a041849","DOIUrl":"https://doi.org/10.1101/cshperspect.a041849","url":null,"abstract":"<p><p>Mitochondria are the masters of evolutionary tinkering, which can be exemplified by both the remarkable variability of the mitochondrial genome architectures and numerous noncanonical features involved in the mitochondrial gene expression. Evolutionary experimentation in these living test tubes is facilitated by their polyploid nature and resulted in a number of surprising oddities identified in various eukaryotic lineages. Excellent examples of these peculiarities are provided by mitochondrial genetic systems of unicellular fungi classified as the budding yeasts. Perhaps the most perplexing eccentricity found in yeast mitochondria are the bypassing elements (byps) residing in the reading frames of protein-coding genes. Ribosomes ignore byps during translation by means of programmed translational bypassing. Massive occurrence of these coding gaps in certain yeast species raises the questions on their evolutionary origin and mobility as well as the molecular mechanism of translational bypassing.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101512","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
Neighboring Cells as Living Substrates for Guiding Collective Cell Migration during Development. 邻近细胞作为指导发育过程中集体细胞迁移的活基质。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-19 DOI: 10.1101/cshperspect.a041741
Hoang Anh Le, Roberto Mayor
{"title":"Neighboring Cells as Living Substrates for Guiding Collective Cell Migration during Development.","authors":"Hoang Anh Le, Roberto Mayor","doi":"10.1101/cshperspect.a041741","DOIUrl":"https://doi.org/10.1101/cshperspect.a041741","url":null,"abstract":"<p><p>As cells migrate inside the body, they encounter various biochemical and physical cues that provide them with directional guidance. In the past 20 years or so, there has been a significant shift in the effort to understand how physical factors contribute to cellular behaviors. Nevertheless, much of the research has been focused on the interactions between migrating cells and the extracellular matrix in vitro as these are simpler and more accessible models, while neglecting the importance of the cellular environment, which often requires in vivo model systems. With the development of new technology along with the appropriate choice of model organisms, the interesting topic of cell-on-cell interaction during migration is beginning to unravel. In this review, we will take a deep dive into some of the recent results that demonstrate how the biophysics of the cellular environment can impact cell migration, with a strong focus on the use of in vivo model systems, naming the <i>Drosophila</i> border cells, the <i>Xenopus</i> cephalic neural crest, and the zebrafish posterior lateral line primordium.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101468","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
The Blood-Brain Barrier: Composition, Properties, and Roles in Brain Health. 血脑屏障：血脑屏障：组成、特性和在大脑健康中的作用。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041422
Baptiste Lacoste, Alexandre Prat, Moises Freitas-Andrade, Chenghua Gu
{"title":"The Blood-Brain Barrier: Composition, Properties, and Roles in Brain Health.","authors":"Baptiste Lacoste, Alexandre Prat, Moises Freitas-Andrade, Chenghua Gu","doi":"10.1101/cshperspect.a041422","DOIUrl":"10.1101/cshperspect.a041422","url":null,"abstract":"<p><p>Blood vessels are critical to deliver oxygen and nutrients to tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier (BBB), which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and protects the neural tissue from toxins and pathogens, and alterations of this barrier are important components of the pathogenesis and progression of various neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the brain endothelial cells (ECs) that form the walls of the blood vessels. These properties are regulated by interactions between different vascular, perivascular, immune, and neural cells. Understanding how these cell populations interact to regulate barrier properties is essential for understanding how the brain functions in both health and disease contexts.</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/PMC12047665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476126","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
Mitochondrial Maintenance in Skeletal Muscle. 骨骼肌中的线粒体维护
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041514
Laura M de Smalen, Christoph Handschin
{"title":"Mitochondrial Maintenance in Skeletal Muscle.","authors":"Laura M de Smalen, Christoph Handschin","doi":"10.1101/cshperspect.a041514","DOIUrl":"10.1101/cshperspect.a041514","url":null,"abstract":"<p><p>Skeletal muscle is one of the tissues with the highest range of variability in metabolic rate, which, to a large extent, is critically dependent on tightly controlled and fine-tuned mitochondrial activity. Besides energy production, other mitochondrial processes, including calcium buffering, generation of heat, redox and reactive oxygen species homeostasis, intermediate metabolism, substrate biosynthesis, and anaplerosis, are essential for proper muscle contractility and performance. It is thus not surprising that adequate mitochondrial function is ensured by a plethora of mechanisms, aimed at balancing mitochondrial biogenesis, proteostasis, dynamics, and degradation. The fine-tuning of such maintenance mechanisms ranges from proper folding or degradation of individual proteins to the elimination of whole organelles, and in extremis, apoptosis of cells. In this review, the present knowledge on these processes in the context of skeletal muscle biology is summarized. Moreover, existing gaps in knowledge are highlighted, alluding to potential future studies and therapeutic implications.</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/PMC7617582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459789","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
Neuronal Circuit Evolution: From Development to Structure and Adaptive Significance. 神经元回路进化：从发育到结构和适应意义。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041493
Nikolaos Konstantinides, Claude Desplan
{"title":"Neuronal Circuit Evolution: From Development to Structure and Adaptive Significance.","authors":"Nikolaos Konstantinides, Claude Desplan","doi":"10.1101/cshperspect.a041493","DOIUrl":"10.1101/cshperspect.a041493","url":null,"abstract":"<p><p>Neuronal circuits represent the functional units of the brain. Understanding how the circuits are generated to perform computations will help us understand how the brain functions. Nevertheless, neuronal circuits are not engineered, but have formed through millions of years of animal evolution. We posit that it is necessary to study neuronal circuit evolution to comprehensively understand circuit function. Here, we review our current knowledge regarding the mechanisms that underlie circuit evolution. First, we describe the possible genetic and developmental mechanisms that have contributed to circuit evolution. Then, we discuss the structural changes of circuits during evolution and how these changes affected circuit function. Finally, we try to put circuit evolution in an ecological context and assess the adaptive significance of specific examples. We argue that, thanks to the advent of new tools and technologies, evolutionary neurobiology now allows us to address questions regarding the evolution of circuitry and behavior that were unimaginable until very recently.</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/PMC11688512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476125","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
Forces Shaping the Blastocyst. 塑造囊胚的力量
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041519
David Rozema, Jean-Léon Maître
{"title":"Forces Shaping the Blastocyst.","authors":"David Rozema, Jean-Léon Maître","doi":"10.1101/cshperspect.a041519","DOIUrl":"10.1101/cshperspect.a041519","url":null,"abstract":"<p><p>The blastocyst forms during the first days of mammalian development. The structure of the blastocyst is conserved among placental mammals and is paramount to the establishment of the first mammalian lineages. The blastocyst is composed of an extraembryonic epithelium, the trophectoderm (TE), that envelopes a fluid-filled lumen and the inner cell mass (ICM). To shape the blastocyst, embryos transit through three stages driven by forces that have been characterized in the mouse embryo over the past decade. The morphogenetically quiescent cleavage stages mask dynamic cytoskeletal remodeling. Then, during the formation of the morula, cells pull themselves together and the strongest ones internalize. Finally, the blastocyst forms after the pressurized lumen breaks the radial symmetry of the embryo before expanding in cycles of collapses and regrowth. In this review, we delineate the force patterns sculpting the blastocyst, based on our knowledge on the mouse and, to some extent, human embryos.</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/PMC12047664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476124","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
Machine Learning for Protein Science and Engineering. 蛋白质科学与工程的机器学习。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-05-05 DOI: 10.1101/cshperspect.a041877
Peter K Koo, Christian Dallago, Ananthan Nambiar, Kevin K Yang
{"title":"Machine Learning for Protein Science and Engineering.","authors":"Peter K Koo, Christian Dallago, Ananthan Nambiar, Kevin K Yang","doi":"10.1101/cshperspect.a041877","DOIUrl":"https://doi.org/10.1101/cshperspect.a041877","url":null,"abstract":"<p><p>Recent years have seen significant breakthroughs at the intersection of machine learning and protein science. Tools such as AlphaFold have revolutionized protein structure prediction. They are also enabling variant effect prediction and functional annotation of proteins, as well as opening up new possibilities for protein design. However, these technological advances must be balanced with sustainable computing practices.</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":"143971753","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
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