journal
https://read.qxmd.com/read/38614098/direct-observation-of-a-condensate-effect-on-super-enhancer-controlled-gene-bursting
#1
Manyu Du, Simon Hendrik Stitzinger, Jan-Hendrik Spille, Won-Ki Cho, Choongman Lee, Mohammed Hijaz, Andrea Quintana, Ibrahim I Cissé
No abstract text is available yet for this article.
April 12, 2024: Cell
https://read.qxmd.com/read/38608703/a-glycolytic-metabolite-bypasses-two-hit-tumor-suppression-by-brca2
#2
JOURNAL ARTICLE
Li Ren Kong, Komal Gupta, Andy Jialun Wu, David Perera, Roland Ivanyi-Nagy, Syed Moiz Ahmed, Tuan Zea Tan, Shawn Lu-Wen Tan, Alessandra Fuddin, Elayanambi Sundaramoorthy, Grace Shiqing Goh, Regina Tong Xin Wong, Ana S H Costa, Callum Oddy, Hannan Wong, C Pawan K Patro, Yun Suen Kho, Xiao Zi Huang, Joan Choo, Mona Shehata, Soo Chin Lee, Boon Cher Goh, Christian Frezza, Jason J Pitt, Ashok R Venkitaraman
Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers...
April 8, 2024: Cell
https://read.qxmd.com/read/38614100/rna-genome-packaging-and-capsid-assembly-of-bluetongue-virus-visualized-in-host-cells
#3
JOURNAL ARTICLE
Xian Xia, Po-Yu Sung, Michael W Martynowycz, Tamir Gonen, Polly Roy, Z Hong Zhou
Unlike those of double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and ssRNA viruses, the mechanism of genome packaging of dsRNA viruses is poorly understood. Here, we combined the techniques of high-resolution cryoelectron microscopy (cryo-EM), cellular cryoelectron tomography (cryo-ET), and structure-guided mutagenesis to investigate genome packaging and capsid assembly of bluetongue virus (BTV), a member of the Reoviridae family of dsRNA viruses. A total of eleven assembly states of BTV capsid were captured, with resolutions up to 2...
April 5, 2024: Cell
https://read.qxmd.com/read/38614099/itpripl1-binds-cd3%C3%AE%C2%B5-to-impede-t%C3%A2-cell-activation-and-enable-tumor-immune-evasion
#4
JOURNAL ARTICLE
Shouyan Deng, Yibo Zhang, Huanbin Wang, Wenhua Liang, Lu Xie, Ning Li, Yuan Fang, Yiting Wang, Jiayang Liu, Hao Chi, Yufan Sun, Rui Ye, Lishen Shan, Jiawei Shi, Zan Shen, Yonggang Wang, Shuhang Wang, Jean-Philippe Brosseau, Feng Wang, Grace Liu, Yingfei Quan, Jie Xu
Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation...
April 5, 2024: Cell
https://read.qxmd.com/read/38608704/chromatin-context-dependent-regulation-and-epigenetic-manipulation-of-prime-editing
#5
JOURNAL ARTICLE
Xiaoyi Li, Wei Chen, Beth K Martin, Diego Calderon, Choli Lee, Junhong Choi, Florence M Chardon, Troy A McDiarmid, Riza M Daza, Haedong Kim, Jean-Benoît Lalanne, Jenny F Nathans, David S Lee, Jay Shendure
We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target site and edit. Position effects on prime editing efficiency are well predicted by chromatin marks, e.g., positively by H3K79me2 and negatively by H3K9me3...
April 5, 2024: Cell
https://read.qxmd.com/read/38604175/time-series-reconstruction-of-the-molecular-architecture-of-human-centriole-assembly
#6
JOURNAL ARTICLE
Marine H Laporte, Davide Gambarotto, Éloïse Bertiaux, Lorène Bournonville, Vincent Louvel, José M Nunes, Susanne Borgers, Virginie Hamel, Paul Guichard
Centriole biogenesis, as in most organelle assemblies, involves the sequential recruitment of sub-structural elements that will support its function. To uncover this process, we correlated the spatial location of 24 centriolar proteins with structural features using expansion microscopy. A time-series reconstruction of protein distributions throughout human procentriole assembly unveiled the molecular architecture of the centriole biogenesis steps. We found that the process initiates with the formation of a naked cartwheel devoid of microtubules...
April 5, 2024: Cell
https://read.qxmd.com/read/38599211/a-pan-cancer-analysis-of-the-microbiome-in-metastatic-cancer
#7
JOURNAL ARTICLE
Thomas W Battaglia, Iris L Mimpen, Joleen J H Traets, Arne van Hoeck, Laurien J Zeverijn, Birgit S Geurts, Gijs F de Wit, Michaël Noë, Ingrid Hofland, Joris L Vos, Sten Cornelissen, Maartje Alkemade, Annegien Broeks, Charlotte L Zuur, Edwin Cuppen, Lodewyk Wessels, Joris van de Haar, Emile Voest
Microbial communities are resident to multiple niches of the human body and are important modulators of the host immune system and responses to anticancer therapies. Recent studies have shown that complex microbial communities are present within primary tumors. To investigate the presence and relevance of the microbiome in metastases, we integrated mapping and assembly-based metagenomics, genomics, transcriptomics, and clinical data of 4,160 metastatic tumor biopsies. We identified organ-specific tropisms of microbes, enrichments of anaerobic bacteria in hypoxic tumors, associations between microbial diversity and tumor-infiltrating neutrophils, and the association of Fusobacterium with resistance to immune checkpoint blockade (ICB) in lung cancer...
April 5, 2024: Cell
https://read.qxmd.com/read/38614101/ninj1-mediates-plasma-membrane-rupture-by-cutting-and-releasing-membrane-disks
#8
JOURNAL ARTICLE
Liron David, Jazlyn P Borges, L Robert Hollingsworth, Allen Volchuk, Isabelle Jansen, Evelyn Garlick, Benjamin E Steinberg, Hao Wu
The membrane protein NINJ1 mediates plasma membrane rupture in pyroptosis and other lytic cell death pathways. Here, we report the cryo-EM structure of a NINJ1 oligomer segmented from NINJ1 rings. Each NINJ1 subunit comprises amphipathic (⍺1, ⍺2) and transmembrane (TM) helices (⍺3, ⍺4) and forms a chain of subunits, mainly by the TM helices and ⍺1. ⍺3 and ⍺4 are kinked, and the Gly residues are important for function. The NINJ1 oligomer possesses a concave hydrophobic side that should face the membrane and a convex hydrophilic side formed by ⍺1 and ⍺2, presumably upon activation...
April 2, 2024: Cell
https://read.qxmd.com/read/38569542/charting-the-cellular-biogeography-in-colitis-reveals-fibroblast-trajectories-and-coordinated-spatial-remodeling
#9
JOURNAL ARTICLE
Paolo Cadinu, Kisha N Sivanathan, Aditya Misra, Rosalind J Xu, Davide Mangani, Evan Yang, Joseph M Rone, Katherine Tooley, Yoon-Chul Kye, Lloyd Bod, Ludwig Geistlinger, Tyrone Lee, Randall T Mertens, Noriaki Ono, Gang Wang, Liliana Sanmarco, Francisco J Quintana, Ana C Anderson, Vijay K Kuchroo, Jeffrey R Moffitt, Roni Nowarski
Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1...
April 1, 2024: Cell
https://read.qxmd.com/read/38582080/a-genome-wide-spectrum-of-tandem-repeat-expansions-in-338-963-humans
#10
JOURNAL ARTICLE
Ya Cui, Wenbin Ye, Jason Sheng Li, Jingyi Jessica Li, Eric Vilain, Tamer Sallam, Wei Li
The Genome Aggregation Database (gnomAD), widely recognized as the gold-standard reference map of human genetic variation, has largely overlooked tandem repeat (TR) expansions, despite the fact that TRs constitute ∼6% of our genome and are linked to over 50 human diseases. Here, we introduce the TR-gnomAD (https://wlcb.oit.uci.edu/TRgnomAD), a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries (39.5% non-European samples). TR-gnomAD offers critical insights into ancestry-specific disease prevalence using disparities in TR unit number frequencies among ancestries...
March 28, 2024: Cell
https://read.qxmd.com/read/38582079/human-ipsc-4r-tauopathy-model-uncovers-modifiers-of-tau-propagation
#11
JOURNAL ARTICLE
Celeste Parra Bravo, Alice Maria Giani, Jesus Madero Perez, Zeping Zhao, Yuansong Wan, Avi J Samelson, Man Ying Wong, Alessandro Evangelisti, Ethan Cordes, Li Fan, Pearly Ye, Daphne Zhu, Tatyana Pozner, Maria Mercedes, Tark Patel, Allan Yarahmady, Gillian K Carling, Fredrik H Sterky, Virginia M Y Lee, Edward B Lee, Michael DeTure, Dennis W Dickson, Manu Sharma, Sue-Ann Mok, Wenjie Luo, Mingrui Zhao, Martin Kampmann, Shiaoching Gong, Li Gan
Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity...
March 28, 2024: Cell
https://read.qxmd.com/read/38565142/cancer-slc6a6-mediated-taurine-uptake-transactivates-immune-checkpoint-genes-and-induces-exhaustion-in-cd8-t%C3%A2-cells
#12
JOURNAL ARTICLE
Tianyu Cao, Wenyao Zhang, Qi Wang, Chen Wang, Wanqi Ma, Cangang Zhang, Minghui Ge, Miaomiao Tian, Jia Yu, Anjun Jiao, Liang Wang, Manjiao Liu, Pei Wang, Zhiyu Guo, Yun Zhou, Shuyi Chen, Wen Yin, Jing Yi, Hao Guo, Hua Han, Baojun Zhang, Kaichun Wu, Daiming Fan, Xin Wang, Yongzhan Nie, Yuanyuan Lu, Xiaodi Zhao
Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression...
March 28, 2024: Cell
https://read.qxmd.com/read/38579712/tracing-the-origin-of-alveolar-stem-cells-in-lung-repair-and-regeneration
#13
JOURNAL ARTICLE
Kuo Liu, Xinfeng Meng, Zixin Liu, Muxue Tang, Zan Lv, Xiuzhen Huang, Hengwei Jin, Ximeng Han, Xiuxiu Liu, Wenjuan Pu, Huan Zhu, Bin Zhou
Alveolar type 2 (AT2) cells are stem cells of the alveolar epithelia. Previous genetic lineage tracing studies reported multiple cellular origins for AT2 cells after injury. However, conventional lineage tracing based on Cre-loxP has the limitation of non-specific labeling. Here, we introduced a dual recombinase-mediated intersectional genetic lineage tracing approach, enabling precise investigation of AT2 cellular origins during lung homeostasis, injury, and repair. We found AT1 cells, being terminally differentiated, did not contribute to AT2 cells after lung injury and repair...
March 27, 2024: Cell
https://read.qxmd.com/read/38574728/infant-microbes-and-metabolites-point-to-childhood-neurodevelopmental-disorders
#14
JOURNAL ARTICLE
Angelica P Ahrens, Tuulia Hyötyläinen, Joseph R Petrone, Kajsa Igelström, Christian D George, Timothy J Garrett, Matej Orešič, Eric W Triplett, Johnny Ludvigsson
This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism...
March 27, 2024: Cell
https://read.qxmd.com/read/38554707/barcoding-of-episodic-memories-in-the-hippocampus-of-a-food-caching-bird
#15
JOURNAL ARTICLE
Selmaan N Chettih, Emily L Mackevicius, Stephanie Hale, Dmitriy Aronov
The hippocampus is critical for episodic memory. Although hippocampal activity represents place and other behaviorally relevant variables, it is unclear how it encodes numerous memories of specific events in life. To study episodic coding, we leveraged the specialized behavior of chickadees-food-caching birds that form memories at well-defined moments in time whenever they cache food for subsequent retrieval. Our recordings during caching revealed very sparse, transient barcode-like patterns of firing across hippocampal neurons...
March 22, 2024: Cell
https://read.qxmd.com/read/38554706/the-spata5-spata5l1-atpase-complex-directs-replisome-proteostasis-to-ensure-genome-integrity
#16
JOURNAL ARTICLE
Vidhya Krishnamoorthy, Martina Foglizzo, Robert L Dilley, Angela Wu, Arindam Datta, Parul Dutta, Lisa J Campbell, Oksana Degtjarik, Laura J Musgrove, Antonio N Calabrese, Elton Zeqiraj, Roger A Greenberg
Ubiquitin-dependent unfolding of the CMG helicase by VCP/p97 is required to terminate DNA replication. Other replisome components are not processed in the same fashion, suggesting that additional mechanisms underlie replication protein turnover. Here, we identify replisome factor interactions with a protein complex composed of AAA+ ATPases SPATA5-SPATA5L1 together with heterodimeric partners C1orf109-CINP (55LCC). An integrative structural biology approach revealed a molecular architecture of SPATA5-SPATA5L1 N-terminal domains interacting with C1orf109-CINP to form a funnel-like structure above a cylindrically shaped ATPase motor...
March 22, 2024: Cell
https://read.qxmd.com/read/38552624/mastigoneme-structure-reveals-insights-into-the-o-linked-glycosylation-code-of-native-hydroxyproline-rich-helices
#17
JOURNAL ARTICLE
Jin Dai, Meisheng Ma, Qingwei Niu, Robyn J Eisert, Xiangli Wang, Poulomi Das, Karl F Lechtreck, Susan K Dutcher, Rui Zhang, Alan Brown
Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices...
March 22, 2024: Cell
https://read.qxmd.com/read/38569543/gut-microbiome-and-metabolome-profiling-in-framingham-heart-study-reveals-cholesterol-metabolizing-bacteria
#18
JOURNAL ARTICLE
Chenhao Li, Martin Stražar, Ahmed M T Mohamed, Julian A Pacheco, Rebecca L Walker, Tina Lebar, Shijie Zhao, Julia Lockart, Andrea Dame, Kumar Thurimella, Sarah Jeanfavre, Eric M Brown, Qi Yan Ang, Brittany Berdy, Dallis Sergio, Rachele Invernizzi, Antonio Tinoco, Gleb Pishchany, Ramachandran S Vasan, Emily Balskus, Curtis Huttenhower, Hera Vlamakis, Clary Clish, Stanley Y Shaw, Damian R Plichta, Ramnik J Xavier
Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition...
March 21, 2024: Cell
https://read.qxmd.com/read/38552625/flexible-scaffold-based-cheminformatics-approach-for-polypharmacological-drug-design
#19
JOURNAL ARTICLE
Zhangcheng Chen, Jing Yu, Huan Wang, Peiyu Xu, Luyu Fan, Fengxiu Sun, Sijie Huang, Pei Zhang, He Huang, Shuo Gu, Bowen Zhang, Yue Zhou, Xiaobo Wan, Gang Pei, H Eric Xu, Jianjun Cheng, Sheng Wang
Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2A R to act as an antagonist and a "stretching-up" binding pose at 5-HT1A R to function as an agonist...
March 21, 2024: Cell
https://read.qxmd.com/read/38552623/short-distance-vesicle-transport-via-phase-separation
#20
JOURNAL ARTICLE
Hua Qiu, Xiandeng Wu, Xiaoli Ma, Shulin Li, Qixu Cai, Marcelo Ganzella, Liang Ge, Hong Zhang, Mingjie Zhang
In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional needs in subcellular compartments but with unknown mechanisms. Such short-distance vesicle transport does not involve molecular motors. Here, we demonstrate, using synaptic vesicle (SV) transport as a paradigm, that phase separation of synaptic proteins with vesicles can facilitate regulated, directional vesicle transport between different presynaptic bouton sub-compartments...
March 21, 2024: Cell
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