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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
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
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