Cell genomics最新文献

{"title":"Single-cell analysis of Barrett's esophagus and carcinoma reveals cell types conferring risk via genetic predisposition.","authors":"Marten C Wenzel, Pouria Dasmeh, Patrick S Plum, Ann-Sophie Giel, Sascha Hoppe, Marek Franitza, Christoph Jonas, René Thieme, Yue Zhao, Dominik Heider, Claire Palles, Rebecca Claire Fitzgerald, Christiane J Bruns, Reinhard Buettner, Alexander Quaas, Ines Gockel, Carlo Maj, Seung-Hun Chon, Johannes Schumacher, Axel M Hillmer","doi":"10.1016/j.xgen.2025.100980","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100980","url":null,"abstract":"<p><p>Inherited genetic variants contribute to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but it is unknown which cell types are involved in this process. We performed single-cell RNA sequencing of BE, EAC, and paired normal tissues and integrated genome-wide association data to determine cell-type-specific genetic risk and cellular processes that contribute to BE and EAC. The analysis reveals that EAC development is driven to a greater extent by local cellular processes than BE development and suggests that one cell type of BE origin (intestinal metaplasia cells) and cellular processes that control the differentiation of columnar cells are of particular relevance for EAC development. Specific subtypes of fibroblasts and endothelial cells likely contribute to BE and EAC development, while dendritic cells and CD4⁺ memory T cells seem to contribute to BE development. The diagnostic value of markers characterizing the cell types and cellular processes should be explored for EAC prediction.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100980"},"PeriodicalIF":11.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci.","authors":"Ke Zhao, Yao Zhou, Xueqi Wang, Zhao Wang, Xinran Xu, Yichen Chen, Lin Zhao, Chengyue Wu, Jianhua Wang, Hongcheng Yao, Xin Cheng, Wei Wang, Xinlei Chu, Weixin Wang, Xianfu Yi, Yupeng Chen, Miaoxin Li, Wange Lu, Kexin Chen, Pak Chung Sham, Dandan Huang, Jing Zhang, Mulin Jun Li","doi":"10.1016/j.xgen.2025.100982","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100982","url":null,"abstract":"<p><p>Most genetic loci linked to polygenic traits are in non-coding regions, with complex regulation and linkage disequilibrium (LD), complicating causal variant and gene prioritization. We used multiplexed single-cell CRISPR interference and activation perturbations to investigate cis-regulatory element (CRE) and gene expression relationships within tight LD in the endogenous chromatin context. We demonstrated the prevalence of multiple causality in perfect LD (pLD) for independent expression quantitative trait loci (eQTLs) and uncovered fine-grained genetic effects on gene expression within pLD, which are difficult to decipher using traditional eQTL fine-mapping or existing computational methods. We found that over one-third of the causal CREs lack classical epigenetic markers prior to perturbation, and we functionally validated one of these hidden regulatory mechanisms. Leveraging Multiome single-cell epigenetic and sequence perturbations, we highlighted the regulatory plasticity of the human genome. Our study will guide the exploration of missing causal mechanisms underlying molecular trait regulation and disease development.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100982"},"PeriodicalIF":11.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematically investigating and identifying bacteriocins in the human gut microbiome.","authors":"Dengwei Zhang, Yinai Zou, Yuqi Shi, Junliang Zhang, Jing Liu, Gengfan Wu, Jian Zhang, Ying Gao, Muxuan Chen, Yong-Xin Li","doi":"10.1016/j.xgen.2025.100983","DOIUrl":"10.1016/j.xgen.2025.100983","url":null,"abstract":"<p><p>Human gut microbiota produces unmodified bacteriocins, natural antimicrobial peptides that protect against pathogens and regulate host physiology. However, current bioinformatic tools limit the comprehensive investigation of bacteriocins' biosynthesis, obstructing research into their biological functions. Here, we introduce IIBacFinder, a superior analysis pipeline for identifying unmodified class II bacteriocins. Through large-scale bioinformatic analysis and experimental validation, we demonstrate their widespread distribution across the bacterial kingdom, with most being habitat specific. Analyzing over 280,000 bacterial genomes, we reveal the diverse potential of human gut bacteria to produce these bacteriocins. Guided by meta-omics analysis, we synthesized 26 hypothetical bacteriocins from gut commensal species, with 16 showing antibacterial activities. Further ex vivo tests show minimal impact of narrow-spectrum bacteriocins on human fecal microbiota. Our study highlights the huge biosynthetic potential of unmodified bacteriocins in the human gut, paving the way for understanding their biological functions and health implications.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100983"},"PeriodicalIF":11.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINE-1 retrotransposons mediate cis-acting transcriptional control in human pluripotent stem cells and regulate early brain development.","authors":"Anita Adami, Raquel Garza, Patricia Gerdes, Pia A Johansson, Fereshteh Dorazehi, Symela Koutounidou, Laura Castilla-Vallmanya, Diahann A M Atacho, Yogita Sharma, Jenny G Johansson, Oliver Tam, Agnete Kirkeby, Roger A Barker, Molly Gale Hammell, Christopher H Douse, Johan Jakobsson","doi":"10.1016/j.xgen.2025.100979","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100979","url":null,"abstract":"<p><p>Long interspersed nuclear element 1 (L1) retrotransposons represent a vast source of genetic variability. However, mechanistic analysis of whether and how L1s contribute to human developmental programs is lacking, in part due to the challenges associated with specific profiling and manipulation of human L1 expression. Here, we show that thousands of hominoid-specific L1 integrants are expressed in human induced pluripotent stem cells and cerebral organoids. The activity levels of individual L1 promoters vary widely and correlate with an active epigenetic state. Efficient on-target CRISPR interference (CRISPRi) silencing of L1s revealed nearly a hundred co-opted L1-derived chimeric transcripts, and L1 silencing resulted in changes in neural differentiation programs and reduced cerebral organoid size. Together, these data implicate L1s and L1-derived transcripts in hominoid-specific CNS developmental processes.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100979"},"PeriodicalIF":11.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural variation, selection, and diversification of the NPIP gene family from the human pangenome.","authors":"Philip C Dishuck, Katherine M Munson, Alexandra P Lewis, Max L Dougherty, Jason G Underwood, William T Harvey, PingHsun Hsieh, Tomi Pastinen, Evan E Eichler","doi":"10.1016/j.xgen.2025.100977","DOIUrl":"10.1016/j.xgen.2025.100977","url":null,"abstract":"<p><p>The NPIP gene family is among the most positively selected gene families in humans/apes and drives independent duplication in primate lineages. These duplications promote genetic instability, leading to recurrent disease-associated microduplication and microdeletion syndromes. Despite its importance, little is known about its function or variation in humans, as short-read sequencing cannot distinguish high-identity duplications. Using long-read assemblies of 169 human haplotypes, we find extreme variation in the content and organization of NPIP loci. We identify fixed and polymorphic paralogs and observe ongoing positive selection. With long-read RNA sequencing (RNA-seq), we create paralog-specific gene models, the majority of which were not previously documented, and observe paralog-specific tissue specificity. This analysis of an exceptionally dynamic gene family provides candidates for future functional study.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100977"},"PeriodicalIF":11.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.","authors":"Kyuto Sonehara, Rei Watanabe, Yutaka Matsumura, Yuichi Mitsui, Yosuke Ogawa, Kaori Odomari, Saori Sakaue, Shinichi Namba, Mariko Komuro, Mio Edamoto, Junya Watanabe, Tomomitsu Hirota, Noriko Arase, Yuumi Nakamura, Kimiko Nakajima, Takashi Okamoto, Rika Nishikawa, Kenichi Yamamoto, Ken Suzuki, Toshihiro Kishikawa, Ryuya Edahiro, Yuya Shirai, Tatsuhiko Naito, Noah Sasa, Yosuke Ishitsuka, Junichi Furuta, Kayo Kunimoto, Ikko Kajihara, Satoshi Fukushima, Hideaki Miyachi, Hiroyuki Matsue, Masahiro Kamata, Mami Momose, Ippei Miyagawa, Hiroaki Tanaka, Masanobu Ueno, Toshinori Bito, Hiroshi Nagai, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara, Emi Nishida, Koichi Matsuda, Nobuhiro Shojima, Ikuma Nakagawa, Yoshihide Asano, Shinichi Sato, Shinichi Imafuku, Yayoi Tada, Chikako Nishigori, Masatoshi Jinnin, Hironobu Ihn, Akihiko Asahina, Hidehisa Saeki, Toshimasa Yamauchi, Takashi Kadowaki, Tatsuyoshi Kawamura, Shinji Shimada, Ichiro Katayama, Koichiro Higasa, Emiko Noguchi, Shigetoshi Sano, Yoshiya Tanaka, Fumihiko Matsuda, Atsushi Kumanogoh, Mayumi Tamari, Takashi Satoh, Manabu Fujimoto, Akimichi Morita, Yukinori Okada","doi":"10.1016/j.xgen.2025.100978","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100978","url":null,"abstract":"<p><p>Psoriasis vulgaris (PsV) is an immune-mediated inflammatory skin disorder with complex genetic architecture. Most genome-wide association studies (GWASs) of PsV have been limited to analyzing common single-nucleotide variants in Europeans, lacking diversity in the variant spectrum and ancestral background. To investigate the contribution of rare variants (RVs) and structural variants (SVs), we perform a whole-genome sequencing study involving 1,415 PsV cases and 3,968 controls in Japanese. A GWAS signal at IFNLR1 is fine-mapped to a 3.3-kb deletion SV disrupting an epithelium-specific putative enhancer, which is validated by PacBio long-read sequencing. Gene-based RV analyses identify two susceptibility genes: IFIH1 (p = 9.8 × 10^-6) and CERCAM (p = 4.1 × 10^-7). Notably, IL36RN, a causative gene for generalized pustular psoriasis, a rare and lethal multi-systemic inflammatory disorder, is associated with common PsV (p = 1.2 × 10^-4). Finally, Cercam knockout (Cercam^-/-) in an imiquimod-induced psoriasis mouse model aggravates dermatitis with elevated T cell retention in the subepidermis. Our study elucidates the overlooked genetic basis of PsV.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100978"},"PeriodicalIF":11.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genomic history of East Asian Middle Neolithic millet- and rice-agricultural populations.","authors":"Jianxue Xiong, Yu Xu, Guoke Chen, Liping Yang, Yawei Zhou, Yiling Pan, Zhiyou Wang, Jiujiang Bai, Baoshuai Zhang, Guanghui Dong, Jingrong Pei, Xiaomin Yang, Liang Chen, Ningwu Kang, Yangyang Wu, Bangyan Wang, Kongyang Zhu, Panxin Du, Xiaolong Li, Hetong Wen, Xiaolin Ma, Tianyou Bai, Wanfa Gu, Yu Ye, Qian Wu, Xin Chang, Jingze Tan, Lei Gao, Dong Ge, Bicheng Li, Yishi Yang, Weiwei Feng, Yini Yang, Pengfei Sheng, Hailiang Meng, Rui Wang, Jiajing Zheng, Xin Jia, Li Jin, Chuan-Chao Wang, Shaoqing Wen","doi":"10.1016/j.xgen.2025.100976","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100976","url":null,"abstract":"<p><p>The Yellow and Yangtze river basins in China are among the world's oldest independent agricultural centers, known for the domestication of millet and rice, respectively, yet their genetic history is poorly understood. Here, we present genome-wide data from 74 Middle Neolithic genetic samples from these regions, showing marked genetic differentiation but bidirectional gene flow, supporting a demic diffusion model of mixed farming. Yellow River populations exhibit distinct genetic substructures resulting from interactions with surrounding groups during the mid-Neolithic expansion of millet agriculture. Upper Yellow River populations are genetically linked to Tibetan Plateau populations and possess the earliest adaptive EPAS1 haplotype (∼5,800 BP) among modern humans. Meanwhile, Yangtze River rice farmers show genetic affinity with Neolithic to present-day southeast coastal China and Austronesian populations, tracing the origins of proto-Austronesians farther north to the Yangtze River. These findings offer new insights into the impact of mid-Neolithic agricultural expansion on human genetic history.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100976"},"PeriodicalIF":11.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine cf-nucleosomes: A non-invasive window into human physiology and disease.","authors":"Matan Lotem, Israa Sharkia, Batia Azria, Esther Harpenas, Maayan Ormianer, Hadar Rosen, Tal Falick-Michaeli, Nir Friedman","doi":"10.1016/j.xgen.2025.100974","DOIUrl":"10.1016/j.xgen.2025.100974","url":null,"abstract":"<p><p>Urine contains fragments of cell-free DNA (cfDNA) that offer molecular insights into processes within the urinary system and the body. It remains unclear whether these fragments exist as chromatin and retain chromatin modifications from their cells of origin. Here, we employ cell-free chromatin immunoprecipitation followed by sequencing (cfChIP-seq) on human urine to address this issue. We show that cf-nucleosomes can be captured from urine and preserve histone modifications associated with gene activation and repression. Analysis in healthy individuals reveals distinct tissue contributions to urine cf-nucleosomes, including a kidney-derived population not detected in matched exfoliated cells or plasma. This suggests that kidney filtration largely excludes plasma cf-nucleosomes. In patients with bladder cancer, urine cf-nucleosomes reflect tumor-associated transcriptional programs and immune responses. These findings highlight the utility of urine cf-nucleosomes as accessible, non-invasive biomarkers for studying renal physiology and monitoring urinary pathologies.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100974"},"PeriodicalIF":11.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionarily recent transcription factors partake in human cell cycle regulation.","authors":"Cyril Pulver, Romain Forey, Alex R Lederer, Martina Begnis, Olga Rosspopoff, Joana Carlevaro-Fita, Filipe Martins, Evarist Planet, Julien Duc, Charlène Raclot, Sandra Offner, Alexandre Coudray, Arianna Dorschel, Didier Trono","doi":"10.1016/j.xgen.2025.100923","DOIUrl":"10.1016/j.xgen.2025.100923","url":null,"abstract":"<p><p>The cell cycle is a fundamental process in eukaryotic biology and is accordingly controlled by a highly conserved core signaling cascade. However, whether recently evolved proteins also influence this process is unclear. Here, we systematically map the influence of evolutionarily recent transcription factors (TFs) on human cell cycle progression. We find that the genomic targets of select young TFs, many of which belong to the rapidly evolving Krüppel-associated box zinc-finger protein (KZFP) family, exhibit synchronized cell cycle expression. Systematic perturbation studies reveal that silencing recent TFs disrupts normal cell cycle progression, which we experimentally confirm for ZNF519, a simian-restricted KZFP. Furthermore, we show that the therian-specific KZFP ZNF274 sets the cell cycle expression and replication timing of hundreds of clustered genes, many of which are KZFPs. These findings highlight an underappreciated level of lineage specificity in cell cycle regulation.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100923"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptional landscapes of Aedes aegypti midgut and fat body after a bloodmeal.","authors":"Thomas Vial, Hélène Lopez-Maestre, Elodie Couderc, Silvain Pinaud, Virginia Howick, Jewelna Akorli, Mara Lawniczak, Guillaume Marti, Sarah Hélène Merkling","doi":"10.1016/j.xgen.2025.100924","DOIUrl":"10.1016/j.xgen.2025.100924","url":null,"abstract":"<p><p>Aedes aegypti mosquitoes transmit arboviruses that pose a growing global health threat. After a bloodmeal, mosquitoes experience complex physiological changes orchestrated by the midgut and fat body, beginning with digestion and culminating in egg production. Our study provides comprehensive midgut and fat-body cell atlases using single-cell RNA sequencing and metabolomics. Our analyses reveal highly diverse cell populations specialized in digestion, metabolism, immunity, and reproduction. The midgut primarily comprises enterocytes, enteroendocrine, and intestinal stem cells, while the fat body features trophocytes and oenocytes but also a substantial hemocyte population and a newly found fat-body-yolk cell population. Additionally, Phasi Charoen-like virus was detected in midgut cells 7 days post bloodmeal. These findings highlight the complexity of mosquito abdominal tissues and inform the development of refined vector-control strategies, focusing on specific cell populations and metabolic pathways essential for mosquito reproductive success.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100924"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}