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Four-Dimensional Bioprinting: Harnessing Active Mechanics to Build with Living Inks. 四维生物打印：利用活性力学构建活墨。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-08-01 DOI: 10.1101/cshperspect.a041557
Honesty Kim, Grace Hu, Austin J Graham, Grace X Gu, Zev J Gartner
{"title":"Four-Dimensional Bioprinting: Harnessing Active Mechanics to Build with Living Inks.","authors":"Honesty Kim, Grace Hu, Austin J Graham, Grace X Gu, Zev J Gartner","doi":"10.1101/cshperspect.a041557","DOIUrl":"10.1101/cshperspect.a041557","url":null,"abstract":"<p><p>Three-dimensional (3D) printing can be beneficial to tissue engineers and the regenerative medicine community because of its potential to rapidly build elaborate 3D structures from cellular and material inks. However, predicting changes to the structure and pattern of printed tissues arising from the mechanical activity of constituent cells is technically and conceptually challenging. This perspective is targeted to scientists and engineers interested in 3D bioprinting, but from the point of view of cells and tissues as mechanically active living materials. The dynamic forces generated by cells present unique challenges compared to conventional manufacturing modalities but also offer profound opportunities through their capacity to self-organize. Consideration of self-organization following 3D printing takes the design and execution of bioprinting into the fourth dimension of cellular activity. We therefore propose a framework for dynamic bioprinting that spatiotemporally guides the underlying biology through reconfigurable material interfaces controlled by 3D printers.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715549","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 Protection in Stem Cells. 干细胞的端粒保护。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-08-01 DOI: 10.1101/cshperspect.a041686
Marta Markiewicz-Potoczny, Eros Lazzerini Denchi
{"title":"Telomere Protection in Stem Cells.","authors":"Marta Markiewicz-Potoczny, Eros Lazzerini Denchi","doi":"10.1101/cshperspect.a041686","DOIUrl":"10.1101/cshperspect.a041686","url":null,"abstract":"<p><p>The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells. In this review, we discuss what is known about the differences between stem cells and somatic cells regarding chromosome end protection.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853184","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
A History of Cancer Research: G1/S Transition and the Retinoblastoma Pathway. 癌症研究的历史：G1/S转变和视网膜母细胞瘤途径。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-08-01 DOI: 10.1101/cshperspect.a035923
Joseph Lipsick
{"title":"A History of Cancer Research: G<sub>1</sub>/S Transition and the Retinoblastoma Pathway.","authors":"Joseph Lipsick","doi":"10.1101/cshperspect.a035923","DOIUrl":"https://doi.org/10.1101/cshperspect.a035923","url":null,"abstract":"<p><p>Basic research that established how the cell cycle is regulated has been critical to our understanding of carcinogenesis and paved the way for new treatments like palbociclib and ribocilib. Mitosis was first observed almost 150 years ago, and the phases of the cell cycle were defined midway through the twentieth century. Subsequent studies in yeast, frogs, mice, and human cells identified the molecular machinery that controls entry into the cell cycle, including cyclin-dependent kinases, their regulators, and the product of the retinoblastoma (RB) gene. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the work that discovered these key molecules and mapped the RB pathway that controls the G<sub>1</sub>/S transition.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"17 8","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764671","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
Zebrafish: Lessons and Insights into Skeletal Muscle Research. 斑马鱼：骨骼肌研究的经验教训和见解。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-28 DOI: 10.1101/cshperspect.a041515
Yansong Lu, Avnika A Ruparelia, Peter D Currie
{"title":"Zebrafish: Lessons and Insights into Skeletal Muscle Research.","authors":"Yansong Lu, Avnika A Ruparelia, Peter D Currie","doi":"10.1101/cshperspect.a041515","DOIUrl":"https://doi.org/10.1101/cshperspect.a041515","url":null,"abstract":"<p><p>Recent technological advances in genome editing capabilities and live imaging capacities have greatly increased the use of the zebrafish model in skeletal muscle research, leading to critical discoveries in the cellular and molecular processes regulating skeletal muscle growth, regeneration, and disease. This is highlighted by the characterization of muscle stem cell and progenitor cell dynamics during growth, the visualization of novel cellular interactions driving regeneration, and the identification of complex disease mechanisms and potential therapies for muscle diseases. This review highlights these latest advancements and discuss the limitations and future directions of zebrafish in skeletal muscle research, focusing on muscle growth, regeneration, and disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728381","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
PIEZO Force Sensors and the Heart. 压电力传感器与心脏。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-28 DOI: 10.1101/cshperspect.a041806
Anna McGrane, Michael Murray, Fiona Bartoli, Marilena Giannoudi, Marcella Conning-Rowland, Leander Stewart, Eylem Levelt, Richard M Cubbon, Erica Dall'Armellina, Kathryn J Griffin, Kate M Herum, Andrew J Smith, David J Beech
{"title":"PIEZO Force Sensors and the Heart.","authors":"Anna McGrane, Michael Murray, Fiona Bartoli, Marilena Giannoudi, Marcella Conning-Rowland, Leander Stewart, Eylem Levelt, Richard M Cubbon, Erica Dall'Armellina, Kathryn J Griffin, Kate M Herum, Andrew J Smith, David J Beech","doi":"10.1101/cshperspect.a041806","DOIUrl":"https://doi.org/10.1101/cshperspect.a041806","url":null,"abstract":"<p><p>The PIEZO1 and PIEZO2 membrane proteins form uniquely structured calcium permeable nonselective cation channels dedicated to mechanical force sensing in eukaryotic cells. In this review of the scientific literature, we address PIEZOs in the heart. PIEZOs enable the formation of the aortic valve, cardiac vasculature, and pericardial drainage. In the established heart, they enable baroreceptor pressure sensing and reflex regulation of the heart rate and influence the heart's size and stiffness through roles in cardiac myocytes and cardiac fibroblasts. Therefore, mechanical force sensing by PIEZOs participates in normal cardiac development and function. There is also interest in PIEZOs in pathophysiology, when the structure and mechanical properties of the heart often change. Studies in rats and mice suggest that experimentally induced cardiac stress and injury cause PIEZO upregulation that is adverse. Similar changes may occur in human heart disease, creating potential for therapeutic benefit through PIEZO modulation. This is a productive, accelerating, and exciting new research topic with importance for our understanding of the heart and its diseases.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728380","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
Blastocrithidia-A Genetic Alien from the Planet Earth. 卵泡卵——来自地球的遗传外星生物。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-28 DOI: 10.1101/cshperspect.a041868
Julius Lukeš, Zuzana Čapková Pavlíková, Vyacheslav Yurchenko, Zdeněk Paris, Leoš Shivaya Valášek
{"title":"<i>Blastocrithidia</i>-A Genetic Alien from the Planet Earth.","authors":"Julius Lukeš, Zuzana Čapková Pavlíková, Vyacheslav Yurchenko, Zdeněk Paris, Leoš Shivaya Valášek","doi":"10.1101/cshperspect.a041868","DOIUrl":"https://doi.org/10.1101/cshperspect.a041868","url":null,"abstract":"<p><p>The standard genetic code, which applies almost without exception, is the key to our understanding of molecular biological processes. Although it is close to impossible to imagine that sparse code changes occur naturally given proteomic constraints, specific cases of codon usage alterations have been documented, mostly in unicellular eukaryotes. Here, we summarize what we have learned about <i>Blastocrithidia</i>, a little-known parasitic flagellate with all three stop codons reassigned to sense codons, which uses UAA as the only universal stop codon. We first describe its origin, life cycle, morphology, cultivation, and transformation, the combination of which predisposes it to become the first tractable eukaryote with a noncanonical genetic code. Next, we present our across-the-genome analysis revealing uneven distribution of in-frame stops and discuss the features distinguishing in-frame and genuine stop codons that allow for so-called position-specific termination. Finally, given what is known about stop codon readthrough by near-cognate transfer RNAs (tRNAs) and the fidelity of stop codon recognition by eukaryotic release factor 1 (eRF1), we propose a model illuminating how unique properties of <i>Blastocrithidia</i> tRNAs, combined with specific alterations of its eRF1, enable this massive deviation from the standard genetic code.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728378","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
Collaboration of Antipodes: Synergy of Branched and Linear F-Actin during Amoeboid Cell Movement and Chemotaxis. 对跖体的协作：分支和线状f -肌动蛋白在变形虫细胞运动和趋化过程中的协同作用。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-28 DOI: 10.1101/cshperspect.a041790
Peter J M van Haastert, Arjan Kortholt
{"title":"Collaboration of Antipodes: Synergy of Branched and Linear F-Actin during Amoeboid Cell Movement and Chemotaxis.","authors":"Peter J M van Haastert, Arjan Kortholt","doi":"10.1101/cshperspect.a041790","DOIUrl":"https://doi.org/10.1101/cshperspect.a041790","url":null,"abstract":"<p><p>The actin cytoskeleton plays a major role in locomotion of amoeboid cells. The extending pseudopod contains predominantly branched F-actin nucleated by actin-related protein 2/3 (Arp2/3) that is oriented toward the membrane, while the side/back of the cell contains predominantly linear F-actin nucleated by formins that is arranged parallel to the membrane in a contractile network using cross-linkers, membrane anchors, and myosin filaments. During cell movement, branched and linear F-actin have opposite functions: Elongation of branched F-actin filaments leads to pseudopod growth in the front, whereas pseudopod formation is strongly inhibited in areas of the contractile network. On the other hand, branched and linear F-actin also collaborate to optimize locomotion and navigation. Assembly of branched F-actin to induce a new pseudopod in the front also activates linear F-actin in the rest of the cell to inhibit a second pseudopod. Furthermore, linear F-actin at the side/back of the cell and branched F-actin each provide a memory of direction that is highly synergistic to mediate strong persistence of cell movement and sensitive chemotaxis.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728379","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 Human Health and Disease. 人类健康和疾病中的端粒动态。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-01 DOI: 10.1101/cshperspect.a041701
Duncan M Baird
{"title":"Telomere Dynamics in Human Health and Disease.","authors":"Duncan M Baird","doi":"10.1101/cshperspect.a041701","DOIUrl":"10.1101/cshperspect.a041701","url":null,"abstract":"<p><p>Telomere function is critical for genomic stability; in the context of a functional TP53 response, telomere erosion leads to a G<sub>1</sub>/S cell-cycle arrest and the induction of replicative senescence, a process that is considered to underpin the ageing process in long-lived species. Abrogation of the TP53 pathway allows for continued cell division, telomere erosion, and the complete loss of telomere function; the ensuing genomic instability facilitates clonal evolution and malignant progression. Telomeres display extensive length heterogeneity in the population that is established at birth, and this affects the individual risk of a broad range of diseases, including cardiovascular disease and cancer. In this perspective, I discuss telomere length heterogeneity at the levels of the population, individual, and cell, and consider how the dynamics of these essential chromosomal structures contribute to human disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715551","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
A History of Cancer Research: The RAS Pathway. 癌症研究的历史：RAS通路。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-07-01 DOI: 10.1101/cshperspect.a035899
Joseph Lipsick
{"title":"A History of Cancer Research: The RAS Pathway.","authors":"Joseph Lipsick","doi":"10.1101/cshperspect.a035899","DOIUrl":"10.1101/cshperspect.a035899","url":null,"abstract":"<p><p>The <i>RAS</i> oncogene is a crucial driver of a number of cancers. The GTPase it encodes links growth factor receptors with signaling pathways that control cell proliferation. Activating mutations in <i>RAS</i> deregulate these pathways, promoting tumor progression. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the discovery of <i>RAS</i> and the subsequent work that revealed its mechanism of action-from the early work on rat sarcoma viruses to biochemical studies that revealed the role of GTP-GDP exchange and work that characterized downstream MAP kinase cascades in a variety of different organisms.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":"17 7","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539294","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
Leading the Way: Molecular Drivers of Single-Cell Migration. 引领道路：单细胞迁移的分子驱动。
IF 6.9 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-06-30 DOI: 10.1101/cshperspect.a041748
Dong Li, Hui Tu, Huaqing Cai
{"title":"Leading the Way: Molecular Drivers of Single-Cell Migration.","authors":"Dong Li, Hui Tu, Huaqing Cai","doi":"10.1101/cshperspect.a041748","DOIUrl":"https://doi.org/10.1101/cshperspect.a041748","url":null,"abstract":"<p><p>Cell migration plays a central role in a wide range of physiological, developmental, and disease-related processes. Studies using single-cell models, such as <i>Dictyostelium discoideum</i>, have provided important insights into the molecular principles underlying this process. Migrating cells exhibit a polarized morphology, with actin-rich protrusions at the leading edge driving forward motion and an actomyosin network at the trailing edge enabling retraction. While actin polymerization and direct cytoskeletal regulators are essential, a complex network of signaling molecules also play a critical role in cell migration. Initially viewed as part of the directional sensing machinery in guided migration, this signaling network is now also recognized as an integral component of the motility module itself. Its spontaneous activity coordinates with cytoskeletal reorganization, enabling cell migration even in the absence of external cues. This review highlights key cytoskeletal and signaling molecules involved in leading-edge protrusion formation, with an emphasis on findings from <i>Dictyostelium</i> studies. We also discuss recent advances in understanding how these cytoskeletal and signaling molecules organize into excitable networks to regulate cell motility.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526728","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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