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Passage of the HIV capsid cracks the nuclear pore

IF 64.5 1区生物学

Cell Pub Date : 2025-01-17 DOI: 10.1016/j.cell.2024.12.008

Jan Philipp Kreysing, Maziar Heidari, Vojtech Zila, Sergio Cruz-León, Agnieszka Obarska-Kosinska, Vibor Laketa, Lara Rohleder, Sonja Welsch, Jürgen Köfinger, Beata Turoňová, Gerhard Hummer, Hans-Georg Kräusslich, Martin Beck

{"title":"Passage of the HIV capsid cracks the nuclear pore","authors":"Jan Philipp Kreysing, Maziar Heidari, Vojtech Zila, Sergio Cruz-León, Agnieszka Obarska-Kosinska, Vibor Laketa, Lara Rohleder, Sonja Welsch, Jürgen Köfinger, Beata Turoňová, Gerhard Hummer, Hans-Georg Kräusslich, Martin Beck","doi":"10.1016/j.cell.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.008","url":null,"abstract":"Upon infection, human immunodeficiency virus type 1 (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T cells and macrophages. The capsid enters the nuclear pore complex (NPC), driven by interactions with numerous phenylalanine-glycine (FG)-repeat nucleoporins (FG-Nups). Whether NPCs structurally adapt to capsid passage and whether capsids are modified during passage remains unknown, however. Here, we combined super-resolution and correlative microscopy with cryoelectron tomography and molecular simulations to study the nuclear entry of HIV-1 capsids in primary human macrophages. Our data indicate that cytosolically bound cyclophilin A is stripped off capsids entering the NPC, and the capsid hexagonal lattice remains largely intact inside and beyond the central channel. Strikingly, the NPC scaffold rings frequently crack during capsid passage, consistent with computer simulations indicating the need for NPC widening. The unique cone shape of the HIV-1 capsid facilitates its entry into NPCs and helps to crack their rings.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"2 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 biophysical basis for the spreading behavior and limited diffusion of Xist

IF 64.5 1区生物学

Cell Pub Date : 2025-01-16 DOI: 10.1016/j.cell.2024.12.004

Mingrui Ding, Danni Wang, Hui Chen, Barry Kesner, Niklas-Benedikt Grimm, Uri Weissbein, Anna Lappala, Jiying Jiang, Carlos Rivera, Jizhong Lou, Pilong Li, Jeannie T. Lee

{"title":"A biophysical basis for the spreading behavior and limited diffusion of Xist","authors":"Mingrui Ding, Danni Wang, Hui Chen, Barry Kesner, Niklas-Benedikt Grimm, Uri Weissbein, Anna Lappala, Jiying Jiang, Carlos Rivera, Jizhong Lou, Pilong Li, Jeannie T. Lee","doi":"10.1016/j.cell.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.004","url":null,"abstract":"Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome. HNRNPK droplets pull on Xist and internalize the RNA. Once internalized, Xist induces a further phase transition and “softens” the HNRNPK droplet. Xist alters the condensate’s deformability, adhesiveness, and wetting properties in vitro. Other Xist-interacting proteins are internalized and entrapped within the droplet, resulting in a concentration of Xist and protein partners within the condensate. We attribute LLPS to HNRNPK’s RGG and Xist’s repeat B (RepB) motifs. Mutating these motifs causes Xist diffusion, disrupts polycomb recruitment, and precludes the required mixing of chromosomal compartments for Xist’s migration. Thus, we hypothesize that phase transitions in HNRNPK condensates allow Xist to locally concentrate silencing factors and to spread through internal channels of the HNRNPK-encapsulated chromosome.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SMC motor proteins extrude DNA asymmetrically and can switch directions

IF 64.5 1区生物学

Cell Pub Date : 2025-01-16 DOI: 10.1016/j.cell.2024.12.020

Roman Barth, Iain F. Davidson, Jaco van der Torre, Michael Taschner, Stephan Gruber, Jan-Michael Peters, Cees Dekker

引用次数: 0

Long somatic DNA-repeat expansion drives neurodegeneration in Huntington’s disease

IF 64.5 1区生物学

Cell Pub Date : 2025-01-16 DOI: 10.1016/j.cell.2024.11.038

Robert E. Handsaker, Seva Kashin, Nora M. Reed, Steven Tan, Won-Seok Lee, Tara M. McDonald, Kiely Morris, Nolan Kamitaki, Christopher D. Mullally, Neda R. Morakabati, Melissa Goldman, Gabriel Lind, Rhea Kohli, Elisabeth Lawton, Marina Hogan, Kiku Ichihara, Sabina Berretta, Steven A. McCarroll

{"title":"Long somatic DNA-repeat expansion drives neurodegeneration in Huntington’s disease","authors":"Robert E. Handsaker, Seva Kashin, Nora M. Reed, Steven Tan, Won-Seok Lee, Tara M. McDonald, Kiely Morris, Nolan Kamitaki, Christopher D. Mullally, Neda R. Morakabati, Melissa Goldman, Gabriel Lind, Rhea Kohli, Elisabeth Lawton, Marina Hogan, Kiku Ichihara, Sabina Berretta, Steven A. McCarroll","doi":"10.1016/j.cell.2024.11.038","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.038","url":null,"abstract":"In Huntington’s disease (HD), striatal projection neurons (SPNs) degenerate during midlife; the core biological question involves how the disease-causing DNA repeat (CAG)n in the huntingtin (HTT) gene leads to neurodegeneration after decades of biological latency. We developed a single-cell method for measuring this repeat’s length alongside genome-wide RNA expression. We found that the HTT CAG repeat expands somatically from 40–45 to 100–500+ CAGs in SPNs. Somatic expansion from 40 to 150 CAGs had no apparent cell-autonomous effect, but SPNs with 150–500+ CAGs lost positive and then negative features of neuronal identity, de-repressed senescence/apoptosis genes, and were lost. Our results suggest that somatic repeat expansion beyond 150 CAGs causes SPNs to degenerate quickly and asynchronously. We conclude that in HD, at any one time, most neurons have an innocuous but unstable HTT gene and that HD pathogenesis is a DNA process for almost all of a neuron’s life.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Spatiotemporal and genetic cell lineage tracing of endodermal organogenesis at single-cell resolution

IF 64.5 1区生物学

Cell Pub Date : 2025-01-16 DOI: 10.1016/j.cell.2024.12.012

Ke-Ran Li, Pei-Long Yu, Qi-Qi Zheng, Xin Wang, Xuan Fang, Lin-Chen Li, Cheng-Ran Xu

{"title":"Spatiotemporal and genetic cell lineage tracing of endodermal organogenesis at single-cell resolution","authors":"Ke-Ran Li, Pei-Long Yu, Qi-Qi Zheng, Xin Wang, Xuan Fang, Lin-Chen Li, Cheng-Ran Xu","doi":"10.1016/j.cell.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.012","url":null,"abstract":"During early mammalian development, the endoderm germ layer forms the foundation of the respiratory and digestive systems through complex patterning. This intricate process, guided by a series of cell fate decisions, remains only partially understood. Our study introduces innovative genetic tracing codes for 14 distinct endodermal regions using novel mouse strains. By integrating high-throughput and high-precision single-cell RNA sequencing with sophisticated imaging, we detailed the spatiotemporal and genetic lineage differentiation of the endoderm at single-cell resolution. We discovered an unexpected multipotentiality within early endodermal regions, allowing differentiation into various organ primordia. This research illuminates the complex and underestimated phenomenon where endodermal organs develop from multiple origins, prompting a reevaluation of traditional differentiation models. Our findings advance understanding in developmental biology and have significant implications for regenerative medicine and the development of advanced organoid models, providing insights into the intricate mechanisms that guide organogenesis.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"5 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women

IF 64.5 1区生物学

Cell Pub Date : 2025-01-15 DOI: 10.1016/j.cell.2024.12.011

Mykhaylo Usyk, Luke Carlson, Nicolas F. Schlecht, Christopher C. Sollecito, Evan Grassi, Fanua Wiek, Shankar Viswanathan, Howard D. Strickler, Anne Nucci-Sack, Angela Diaz, Robert D. Burk

{"title":"Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women","authors":"Mykhaylo Usyk, Luke Carlson, Nicolas F. Schlecht, Christopher C. Sollecito, Evan Grassi, Fanua Wiek, Shankar Viswanathan, Howard D. Strickler, Anne Nucci-Sack, Angela Diaz, Robert D. Burk","doi":"10.1016/j.cell.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.011","url":null,"abstract":"This study investigated the cervicovaginal microbiome’s (CVM’s) impact on Chlamydia trachomatis (CT) infection among Black and Hispanic adolescent and young adult women. A total of 187 women with incident CT were matched to 373 controls, and the CVM was characterized before, during, and after CT infection. The findings highlight that a specific subtype of bacterial vaginosis (BV), identified from 16S rRNA gene reads using the molBV algorithm and community state type (CST) clustering, is a significant risk factor for CT acquisition. A microbial risk score (MRS) further identified a network of bacterial genera associated with increased CT risk. Post treatment, the CVM associated with CT acquisition re-emerged in a different subset of cases leading to reinfection. Additionally, the analysis showed a connection between post-treatment CVM and the development of pelvic inflammatory disease (PID) and miscarriage, further underscoring the CVM’s contributing role to incident CT natural history and highlighting its consideration as a therapeutic target.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"52 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 gut-lung axis: Protozoa join the party

IF 64.5 1区生物学

Cell Pub Date : 2025-01-15 DOI: 10.1016/j.cell.2024.12.027

Nicola L. Harris, Benjamin J. Marsland

引用次数: 0

Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies 抑郁症跨基因组研究发现了 697 种与细胞类型和药物疗法相关的关联性

IF 64.5 1区生物学

Cell Pub Date : 2025-01-14 DOI: 10.1016/j.cell.2024.12.002

引用次数: 0

Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution

IF 64.5 1区生物学

Cell Pub Date : 2025-01-14 DOI: 10.1016/j.cell.2024.12.005

Jose Espejo Valle-Inclan, Solange De Noon, Katherine Trevers, Hillary Elrick, Ianthe A.E.M. van Belzen, Sonia Zumalave, Carolin M. Sauer, Mélanie Tanguy, Thomas Butters, Francesc Muyas, Alistair G. Rust, Fernanda Amary, Roberto Tirabosco, Adam Giess, Alona Sosinsky, Greg Elgar, Adrienne M. Flanagan, Isidro Cortés-Ciriano

{"title":"Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution","authors":"Jose Espejo Valle-Inclan, Solange De Noon, Katherine Trevers, Hillary Elrick, Ianthe A.E.M. van Belzen, Sonia Zumalave, Carolin M. Sauer, Mélanie Tanguy, Thomas Butters, Francesc Muyas, Alistair G. Rust, Fernanda Amary, Roberto Tirabosco, Adam Giess, Alona Sosinsky, Greg Elgar, Adrienne M. Flanagan, Isidro Cortés-Ciriano","doi":"10.1016/j.cell.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.005","url":null,"abstract":"Osteosarcoma is the most common primary cancer of the bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis is an ongoing mutational process, occurring subclonally in 74% of osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, the ongoing evolution of which drives the acquisition of oncogenic mutations, clonal diversification, and intra-tumor heterogeneity across diverse sarcomas and carcinomas. In addition, we characterize a new mechanism, termed loss-translocation-amplification (LTA) chromothripsis, which mediates punctuated evolution in about half of pediatric and adult high-grade osteosarcomas. LTA chromothripsis occurs when a single double-strand break triggers concomitant TP53 inactivation and oncogene amplification through breakage-fusion-bridge cycles. It is particularly prevalent in osteosarcoma and is not detected in other cancers driven by TP53 mutation. Finally, we identify the level of genome-wide loss of heterozygosity as a strong prognostic indicator for high-grade osteosarcoma.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"22 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Direct visualization of electric-field-stimulated ion conduction in a potassium channel

IF 64.5 1区生物学

Cell Pub Date : 2025-01-09 DOI: 10.1016/j.cell.2024.12.006

BoRam Lee, K. Ian White, Michael Socolich, Margaret A. Klureza, Robert Henning, Vukica Srajer, Rama Ranganathan, Doeke R. Hekstra

引用次数: 0