Cell genomicsPub Date : 2025-08-13Epub Date: 2025-07-07DOI: 10.1016/j.xgen.2025.100927
Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James de Bony de Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin
{"title":"Coordinated regulation by lncRNAs results in tight lncRNA-target couplings.","authors":"Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James de Bony de Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin","doi":"10.1016/j.xgen.2025.100927","DOIUrl":"10.1016/j.xgen.2025.100927","url":null,"abstract":"<p><p>The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to effectively dysregulate cancer programs. As a proof of principle, we studied the regulation of DICER1, a cancer gene that plays a key role in microRNA biogenesis, by the lncRNA ZFAS1. We showed that ZFAS1 helps activate DICER1 transcription and block its mRNA degradation to phenomimic DICER1 and regulate its target microRNAs.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100927"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593054","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-06-17DOI: 10.1016/j.xgen.2025.100918
Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G H Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Lorenz Kretschmer, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Peñalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat H Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering, Marina Botto, Sarah A Teichmann, Muzlifah Haniffa, Menna R Clatworthy, David C Thomas, James E Peters
{"title":"Temporal multi-omics analysis of COVID-19 in end-stage kidney disease.","authors":"Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G H Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Lorenz Kretschmer, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Peñalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat H Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering, Marina Botto, Sarah A Teichmann, Muzlifah Haniffa, Menna R Clatworthy, David C Thomas, James E Peters","doi":"10.1016/j.xgen.2025.100918","DOIUrl":"10.1016/j.xgen.2025.100918","url":null,"abstract":"<p><p>Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100918"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327898","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-07-24DOI: 10.1016/j.xgen.2025.100952
Konstantinos C Makris, Andrea Baccarelli, Edwin K Silverman, Robert O Wright
{"title":"How exposomic tools complement and enrich genomic research.","authors":"Konstantinos C Makris, Andrea Baccarelli, Edwin K Silverman, Robert O Wright","doi":"10.1016/j.xgen.2025.100952","DOIUrl":"10.1016/j.xgen.2025.100952","url":null,"abstract":"<p><p>Because genetics and the environment interact to drive gene expression, we propose that exposomics must now be incorporated into the multi-omics paradigm to complete the overall biological pathway. Exposomics' groundbreaking tools and life-course framework holistically characterize non-genetic (environment) components of chronic diseases and integrate with multi-omics. This work brings forward the importance of the human exposome as a major driver of gene/protein expression across the life course. Exposome features are noteworthy for multi-omics as they (1) show where and when biodynamic trajectories of gene x environment interactions meet; (2) move beyond single-environmental-factor-centric views; (3) integrate exposomic measurements during and outside of critical windows of susceptibility; (4) provide agnostic discovery and hypothesis-generating studies; and (5) are biodynamic over time. Upon applying these unique features of the human exposome, future human studies are anticipated to revolutionize the integration of genetics and environmental health sciences.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100952"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719236","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}
Cell genomicsPub Date : 2025-08-13DOI: 10.1016/j.xgen.2025.100972
Amit Felach, Assaf C Bester
{"title":"Take the bull by the horns: A computational framework to predict lncRNA function.","authors":"Amit Felach, Assaf C Bester","doi":"10.1016/j.xgen.2025.100972","DOIUrl":"10.1016/j.xgen.2025.100972","url":null,"abstract":"<p><p>In this issue of Cell Genomics, Chiu et al.<sup>1</sup> present a new framework, \"BigHorn,\" to predict lncRNA chromatin interactions and show that it can be used to predict lncRNA function. Felach and Bester discuss the findings in this preview article.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 8","pages":"100972"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857145","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":"A rare, evolutionarily conserved venom protein benefits endoparasitism across parasitoids.","authors":"Zhi Dong, Yueqi Lu, Gangqi Fang, Qichao Zhang, Yifeng Sheng, Lan Pang, Jiani Chen, Wenqi Shi, Ting Feng, Junwei Zhang, Yixiang Zhang, Guiyun Li, Xuexin Chen, Jianhua Huang, Shuai Zhan","doi":"10.1016/j.xgen.2025.100920","DOIUrl":"10.1016/j.xgen.2025.100920","url":null,"abstract":"<p><p>Although many venom proteins and other parasitic effectors have been identified in various specific systems of parasitoids, key elements that contribute to parasitic success across a broad range of taxa remain largely unexplored. Here, we focus on Leptopilina and conduct a large-scale, multi-omics study to explore common venom proteins for these drosophilid parasitoids. We find that this genus has undergone extensive chromosome rearrangements and a rapid turnover of venom gene repertoires between species. Interestingly, we identified a lineage-specific venom lipase, Leptopilina-specific venom lipase (LVL), as a rare venom protein that is subject to evolutionary constraint and recruited by all Leptopilina species. Functional genetics studies on LVL reveal its critical role in hydrolyzing host lipids under acidic conditions, which in turn ensures the nutrition supply for the embryonic development of parasitoids. Our study provides a paradigm to characterize adaptive effectors across diverse insects and highlights the importance of host lipid utilization in the parasitization of parasitoids.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100920"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337297","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-07-07DOI: 10.1016/j.xgen.2025.100946
Felix Drost, Anna Chernysheva, Mahmoud Albahah, Katharina Kocher, Kilian Schober, Benjamin Schubert
{"title":"Benchmarking of T cell receptor-epitope predictors with ePytope-TCR.","authors":"Felix Drost, Anna Chernysheva, Mahmoud Albahah, Katharina Kocher, Kilian Schober, Benjamin Schubert","doi":"10.1016/j.xgen.2025.100946","DOIUrl":"10.1016/j.xgen.2025.100946","url":null,"abstract":"<p><p>Understanding the recognition of disease-derived epitopes through T cell receptors (TCRs) has the potential to serve as a stepping stone for the development of efficient immunotherapies and vaccines. While a plethora of sequence-based prediction methods for TCR-epitope binding exists, their pre-trained models have not been comparatively evaluated. To alleviate this shortcoming, we integrated 21 TCR-epitope prediction models into the immune-prediction framework ePytope, offering interoperable interfaces with standard TCR repertoire data formats. We showcase the applicability of ePytope-TCR by evaluating the performance of these publicly available prediction models on two challenging datasets. While novel predictors successfully predicted binding to frequently observed epitopes, all methods failed for less frequently observed epitopes. Further, we detected a strong bias in the prediction scores between different epitope classes. We envision this benchmark to guide researchers in their choice of a predictor and to accelerate the method development by defining standardized evaluation settings.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100946"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593053","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-06-10DOI: 10.1016/j.xgen.2025.100916
Liangliang Liu, Itzel Astiazarán Rascón, Dong Lin, Yuchao Ni, Xin Dong, Hui Xue, Yen-Yi Lin, Anne Haegert, Funda Sar, James W Peacock, Tabitha Tombe, Christopher Dusek, Amina Zoubeidi, Martin E Gleave, Colin Collins, Francois Bénard, Yuzhuo Wang, Christopher J Ong
{"title":"CXCR4-LASP1-G9a-SNAIL axis drives NEPC transdifferentiation via induction of EMT and downregulation of REST.","authors":"Liangliang Liu, Itzel Astiazarán Rascón, Dong Lin, Yuchao Ni, Xin Dong, Hui Xue, Yen-Yi Lin, Anne Haegert, Funda Sar, James W Peacock, Tabitha Tombe, Christopher Dusek, Amina Zoubeidi, Martin E Gleave, Colin Collins, Francois Bénard, Yuzhuo Wang, Christopher J Ong","doi":"10.1016/j.xgen.2025.100916","DOIUrl":"10.1016/j.xgen.2025.100916","url":null,"abstract":"<p><p>Phenotypic switching is an emerging driver of cancer treatment resistance, yet early signals regulating this process remain unclear. Here, using longitudinal single-cell RNA sequencing, we mapped differentiation trajectories in the LTL331 prostate adenocarcinoma patient-derived xenograft (PDX) model undergoing neuroendocrine prostate cancer (NEPC) transformation post castration. Our analyses identified a key differentiation node marked by epithelial-mesenchymal transition (EMT) and repressor element-1 silencing transcription factor (REST) downregulation driven by the CXCR4-LASP1-G9a-SNAIL axis. Mechanistically, CXCR4 activation promotes nuclear translocation of LASP1 that links G9a and SNAIL via SH3/proline-rich motif and LIM/SNAG domain interactions, enabling SNAIL-mediated REST repression via promoter E-box motifs. Inhibition of CXCR4 or G9a reversed LTL331R NEPC cells toward a luminal androgen receptor-active phenotype. CXCR4-targeted radioligands enabled both imaging and inhibition of NEPC tumors in vivo. These findings highlight the CXCR4-LASP1-G9a-SNAIL axis as a key regulator of epigenetic and transcriptional reprogramming in NEPC transdifferentiation and support its therapeutic targeting in aggressive NEPC.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100916"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276917","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-05-29DOI: 10.1016/j.xgen.2025.100891
Alexander L Starr, Toshiya Nishimura, Kyomi J Igarashi, Chihiro Funamoto, Hiromitsu Nakauchi, Hunter B Fraser
{"title":"Disentangling cell-intrinsic and cell-extrinsic factors underlying evolution.","authors":"Alexander L Starr, Toshiya Nishimura, Kyomi J Igarashi, Chihiro Funamoto, Hiromitsu Nakauchi, Hunter B Fraser","doi":"10.1016/j.xgen.2025.100891","DOIUrl":"10.1016/j.xgen.2025.100891","url":null,"abstract":"<p><p>A long-standing question in biology is the extent to which cells function autonomously as opposed to requiring interactions with other cells or environmental factors. Here, we develop a framework to use interspecies chimeras to precisely decompose evolutionary divergence in any cellular trait into cell-intrinsic and cell-extrinsic components. Applying this framework to thousands of gene expression levels in reciprocal rat-mouse chimeras, we found that most divergence is cell intrinsic, though extrinsic factors also play an integral role. For example, cell-extrinsic regulation of a transcription factor can propagate to its target genes, leading to cell-type-specific extrinsic regulation of both their mRNA and their protein levels. We also show that imprinted genes are dramatically misexpressed in chimeras, suggesting a mismatch between rapidly evolving intrinsic and extrinsic imprinting mechanisms. Overall, our conceptual framework opens up new avenues to investigate the mechanistic basis of the evolution, development, and regulation of myriad cellular traits in any multicellular organism.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100891"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188616","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}
Cell genomicsPub Date : 2025-08-13Epub Date: 2025-06-03DOI: 10.1016/j.xgen.2025.100894
Elena Fusari, Mariana Muzzopappa, Juliette Gracia, Marco Milán
{"title":"Depletion of aneuploid cells is shaped by cell-to-cell interactions.","authors":"Elena Fusari, Mariana Muzzopappa, Juliette Gracia, Marco Milán","doi":"10.1016/j.xgen.2025.100894","DOIUrl":"10.1016/j.xgen.2025.100894","url":null,"abstract":"<p><p>Aneuploidy is pervasive in early human embryos but robustly dampened during development. Later in life, aneuploidy correlates with pathological conditions, including cancer. Identification of the mechanisms underlying the elimination of aneuploid cells is relevant in development and disease. We characterized the impact on cell proliferation and survival of a large collection of molecularly defined segmental monosomies and trisomies of different sizes and ranges of overlap. Our data reveal signs of outcompetition of cells carrying small monosomies in regions devoid of previously known haploinsufficient genes. Dose-dependent effects of single genes or a discrete number of genes contribute to the phenomenon of cell competition through different mechanisms. By simultaneously inducing cells carrying monosomies and trisomies of the same genomic location, we show that trisomies potentiate or alleviate the negative effects of monosomy on growth, thus revealing a key role of cell interactions in defining the in vivo elimination of aneuploid cells.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100894"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227826","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}
Cell genomicsPub Date : 2025-08-13DOI: 10.1016/j.xgen.2025.100975
David Gfeller
{"title":"Predicting TCR-epitope recognition: How good are we?","authors":"David Gfeller","doi":"10.1016/j.xgen.2025.100975","DOIUrl":"10.1016/j.xgen.2025.100975","url":null,"abstract":"<p><p>Accurate TCR-epitope interaction predictions have the potential to unlock the use of TCR repertoires for diagnostics, TCR discovery, and cross-reactivity predictions. In this issue of Cell Genomics, Drost et al.<sup>1</sup> developed a streamlined framework for benchmarking such predictions. Careful understanding of the strengths and limitations of existing approaches will be instrumental to improve them and expand the scope of TCR-epitope recognition predictions.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 8","pages":"100975"},"PeriodicalIF":11.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857144","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}