Pub Date : 2026-02-06DOI: 10.1038/s41588-026-02511-3
{"title":"Targeting skull bone marrow hematopoiesis for the treatment of childhood brain tumors.","authors":"","doi":"10.1038/s41588-026-02511-3","DOIUrl":"https://doi.org/10.1038/s41588-026-02511-3","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132335","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}
Pub Date : 2026-02-06DOI: 10.1038/s41588-025-02488-5
{"title":"How chromosome folding records events of a cell's past.","authors":"","doi":"10.1038/s41588-025-02488-5","DOIUrl":"https://doi.org/10.1038/s41588-025-02488-5","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132389","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}
Pub Date : 2026-02-05DOI: 10.1038/s41588-025-02481-y
Marco Medici
{"title":"Polygenic risk scores in thyroid cancer screening, diagnosis and management.","authors":"Marco Medici","doi":"10.1038/s41588-025-02481-y","DOIUrl":"https://doi.org/10.1038/s41588-025-02481-y","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125213","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}
Pub Date : 2026-02-05DOI: 10.1038/s41588-025-02483-w
Samantha L White, Maizy S Brasher, Jack Pattee, Wei Zhou, Sinéad Chapman, Yon Ho Jee, Caitlin C Bell, Taylor L Jamil, Martin Barrio, Christopher H Arehart, Luke M Evans, Jibril Hirbo, Nancy J Cox, Peter Straub, Shinichi Namba, Emily Bertucci-Richter, Lindsay Guare, Ahmed Edris, Sam Morris, Ashley J Mulford, Haoyu Zhang, Brian Fennessy, Martin D Tobin, Jing Chen, Alexander T Williams, Catherine John, David A van Heel, Rohini Mathur, Sarah Finer, Marta R Moksnes, Ben M Brumpton, Bjørn Olav Åsvold, Raitis Peculis, Vita Rovite, Ilze Konrade, Ying Wang, Kristy Crooks, Sameer Chavan, Matthew J Fisher, Nicholas Rafaels, Meng Lin, Jonathan A Shortt, Alan R Sanders, David C Whiteman, Stuart MacGregor, Sarah E Medland, Unnur Thorsteinsdóttir, Kári Stefánsson, Tugce Karaderi, Kathleen M Egan, Therese Bocklage, Hilary C McCrary, Gregory Riedlinger, Bodour Salhia, Craig Shriver, Minh D Phan, Janice L Farlow, Stephen Edge, Varinder Kaur, Michelle L Churchman, Robert J Rounbehler, Pamela L Brock, Matthew D Ringel, Milton Pividori, Rebecca Schweppe, Christopher D Raeburn, Robin G Walters, Zhengming Chen, Liming Li, Koichi Matsuda, Yukinori Okada, Sebastian Zöllner, Anurag Verma, Michael H Preuss, Eimear Kenny, Audrey E Hendricks, Lauren Fishbein, Peter Kraft, Mark J Daly, Benjamin M Neale, Alicia R Martin, Joanne B Cole, Bryan R Haugen, Christopher R Gignoux, Nikita Pozdeyev
Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), benign nodular goiter, Graves' disease, lymphocytic thyroiditis and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 313 known and 570 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, benign nodular goiter and autoimmune thyroid diseases (rg = 0.16-0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with ThC. We propose a paradigm that explains genetic predisposition to benign and malignant thyroid nodules. We found polygenic risk score associations with ThC risk of structural disease recurrence, tumor size, multifocality, lymph node metastases and extranodal extension. Polygenic risk scores identified individuals with aggressive ThC in a biobank, creating an opportunity for genetically informed population screening.
{"title":"Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.","authors":"Samantha L White, Maizy S Brasher, Jack Pattee, Wei Zhou, Sinéad Chapman, Yon Ho Jee, Caitlin C Bell, Taylor L Jamil, Martin Barrio, Christopher H Arehart, Luke M Evans, Jibril Hirbo, Nancy J Cox, Peter Straub, Shinichi Namba, Emily Bertucci-Richter, Lindsay Guare, Ahmed Edris, Sam Morris, Ashley J Mulford, Haoyu Zhang, Brian Fennessy, Martin D Tobin, Jing Chen, Alexander T Williams, Catherine John, David A van Heel, Rohini Mathur, Sarah Finer, Marta R Moksnes, Ben M Brumpton, Bjørn Olav Åsvold, Raitis Peculis, Vita Rovite, Ilze Konrade, Ying Wang, Kristy Crooks, Sameer Chavan, Matthew J Fisher, Nicholas Rafaels, Meng Lin, Jonathan A Shortt, Alan R Sanders, David C Whiteman, Stuart MacGregor, Sarah E Medland, Unnur Thorsteinsdóttir, Kári Stefánsson, Tugce Karaderi, Kathleen M Egan, Therese Bocklage, Hilary C McCrary, Gregory Riedlinger, Bodour Salhia, Craig Shriver, Minh D Phan, Janice L Farlow, Stephen Edge, Varinder Kaur, Michelle L Churchman, Robert J Rounbehler, Pamela L Brock, Matthew D Ringel, Milton Pividori, Rebecca Schweppe, Christopher D Raeburn, Robin G Walters, Zhengming Chen, Liming Li, Koichi Matsuda, Yukinori Okada, Sebastian Zöllner, Anurag Verma, Michael H Preuss, Eimear Kenny, Audrey E Hendricks, Lauren Fishbein, Peter Kraft, Mark J Daly, Benjamin M Neale, Alicia R Martin, Joanne B Cole, Bryan R Haugen, Christopher R Gignoux, Nikita Pozdeyev","doi":"10.1038/s41588-025-02483-w","DOIUrl":"https://doi.org/10.1038/s41588-025-02483-w","url":null,"abstract":"<p><p>Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), benign nodular goiter, Graves' disease, lymphocytic thyroiditis and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 313 known and 570 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, benign nodular goiter and autoimmune thyroid diseases (rg = 0.16-0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with ThC. We propose a paradigm that explains genetic predisposition to benign and malignant thyroid nodules. We found polygenic risk score associations with ThC risk of structural disease recurrence, tumor size, multifocality, lymph node metastases and extranodal extension. Polygenic risk scores identified individuals with aggressive ThC in a biobank, creating an opportunity for genetically informed population screening.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125201","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}
Pub Date : 2026-02-04DOI: 10.1038/s41588-025-02489-4
Flora Paldi, Michael-Florian Szalay, Solène Dufau, Marco Di Stefano, Hadrien Reboul, Daniel Jost, Frédéric Bantignies, Giacomo Cavalli
Epigenetic memory enables the propagation of gene expression patterns following transient stimuli. Although three-dimensional chromatin organization is emerging as a key regulator of genome function, it is unknown whether it contributes to cellular memory. Here we establish that acute perturbation of the epigenome can induce cellular memory of gene expression in mouse embryonic stem cells. We uncover how a pulse of histone deacetylase inhibition translates to changes in transcription, histone modifications and genome folding. While most epigenomic and transcriptional changes are initially reversed once the perturbation is removed, some loci remain transcriptionally deregulated and genome architecture partially maintains its perturbed conformation. Consequently, a second pulse of transient hyperacetylation induces stronger memory of transcriptional deregulation. Using ultradeep Micro-C, we associate memory of gene expression with repressive Polycomb-mediated chromatin topology. These results demonstrate how cells can record transient stresses in their genome architecture, thereby enabling an enhanced response to subsequent perturbations.
{"title":"Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding","authors":"Flora Paldi, Michael-Florian Szalay, Solène Dufau, Marco Di Stefano, Hadrien Reboul, Daniel Jost, Frédéric Bantignies, Giacomo Cavalli","doi":"10.1038/s41588-025-02489-4","DOIUrl":"https://doi.org/10.1038/s41588-025-02489-4","url":null,"abstract":"Epigenetic memory enables the propagation of gene expression patterns following transient stimuli. Although three-dimensional chromatin organization is emerging as a key regulator of genome function, it is unknown whether it contributes to cellular memory. Here we establish that acute perturbation of the epigenome can induce cellular memory of gene expression in mouse embryonic stem cells. We uncover how a pulse of histone deacetylase inhibition translates to changes in transcription, histone modifications and genome folding. While most epigenomic and transcriptional changes are initially reversed once the perturbation is removed, some loci remain transcriptionally deregulated and genome architecture partially maintains its perturbed conformation. Consequently, a second pulse of transient hyperacetylation induces stronger memory of transcriptional deregulation. Using ultradeep Micro-C, we associate memory of gene expression with repressive Polycomb-mediated chromatin topology. These results demonstrate how cells can record transient stresses in their genome architecture, thereby enabling an enhanced response to subsequent perturbations.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"88 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115843","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}
Pub Date : 2026-02-04DOI: 10.1038/s41588-025-02491-w
Saranya Arirangan, Leticia F. de Oliveira, Md Nazmul Hasan, Autumn B. Sherman, Mitchell Tuinstra, Luiz F. Brito, Robbee Wedow, Matthew Tegtmeyer
{"title":"Sharing approaches in predictive genomics across animals, plants and humans","authors":"Saranya Arirangan, Leticia F. de Oliveira, Md Nazmul Hasan, Autumn B. Sherman, Mitchell Tuinstra, Luiz F. Brito, Robbee Wedow, Matthew Tegtmeyer","doi":"10.1038/s41588-025-02491-w","DOIUrl":"https://doi.org/10.1038/s41588-025-02491-w","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"234 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115842","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}
Pub Date : 2026-02-03DOI: 10.1038/s41588-025-02486-7
Yuxin Zou, Peter Carbonetto, Dongyue Xie, Gao Wang, Matthew Stephens
We introduce mvSuSiE, a multitrait fine-mapping method, to identify putative causal variants from genetic association data (individual-level or summary). mvSuSiE learns patterns of shared genetic effects from data, and exploits these patterns to improve power to identify causal single nucleotide polymorphisms (SNPs). Comparisons on simulated data show that mvSuSiE is competitive in speed, power and precision with existing multitrait methods, and uniformly improves over single-trait fine-mapping (Sum of Single Effects) performed separately for each trait. We applied mvSuSiE to jointly fine-map 16 blood cell traits using data from the UK Biobank. By jointly analyzing traits and modeling heterogeneous effect-sharing patterns, we identified a substantially larger number of causal SNPs (>3,000) than single-trait fine-mapping and achieved narrower credible sets. mvSuSiE also more comprehensively characterized how genetic variants affect blood cell traits; 68% of causal SNPs showed significant effects across more than one blood cell type.
我们引入了mvSuSiE，一种多性状精细定位方法，从遗传关联数据（个体水平或汇总水平）中识别假定的因果变异。mvSuSiE从数据中学习共享遗传效应的模式，并利用这些模式来提高识别因果单核苷酸多态性（snp）的能力。仿真数据的比较表明，mvSuSiE在速度、功率和精度方面与现有的多性状方法具有竞争力，并且比单个性状单独进行的单性状精细映射（Sum of Single Effects）有统一的提高。我们利用英国生物银行（UK Biobank）的数据，应用mvSuSiE共同绘制了16种血细胞特征的精细图谱。通过共同分析性状和建模异质效应共享模式，我们确定了比单性状精细映射多得多的因果snp（约3000个），并获得了更窄的可信集。mvSuSiE还更全面地描述了基因变异如何影响血细胞特征；68%的因果snp在一种以上的血细胞类型中显示出显著影响。
{"title":"Fast and flexible joint fine-mapping of multiple traits via the Sum of Single Effects model","authors":"Yuxin Zou, Peter Carbonetto, Dongyue Xie, Gao Wang, Matthew Stephens","doi":"10.1038/s41588-025-02486-7","DOIUrl":"https://doi.org/10.1038/s41588-025-02486-7","url":null,"abstract":"We introduce mvSuSiE, a multitrait fine-mapping method, to identify putative causal variants from genetic association data (individual-level or summary). mvSuSiE learns patterns of shared genetic effects from data, and exploits these patterns to improve power to identify causal single nucleotide polymorphisms (SNPs). Comparisons on simulated data show that mvSuSiE is competitive in speed, power and precision with existing multitrait methods, and uniformly improves over single-trait fine-mapping (Sum of Single Effects) performed separately for each trait. We applied mvSuSiE to jointly fine-map 16 blood cell traits using data from the UK Biobank. By jointly analyzing traits and modeling heterogeneous effect-sharing patterns, we identified a substantially larger number of causal SNPs (>3,000) than single-trait fine-mapping and achieved narrower credible sets. mvSuSiE also more comprehensively characterized how genetic variants affect blood cell traits; 68% of causal SNPs showed significant effects across more than one blood cell type.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"23 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102127","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}
Pub Date : 2026-02-03DOI: 10.1038/s41588-025-02485-8
Nora I. Strom, Brad Verhulst, Silviu-Alin Bacanu, Rosa Cheesman, Kirstin L. Purves, Hüseyin Gedik, Brittany L. Mitchell, Alex S. Kwong, Annika B. Faucon, Kritika Singh, Sarah Medland, Lucia Colodro-Conde, Kristi Krebs, Per Hoffmann, Stefan Herms, Jan Gehlen, Stephan Ripke, Swapnil Awasthi, Teemu Palviainen, Elisa M. Tasanko, Roseann E. Peterson, Daniel E. Adkins, Andrey A. Shabalin, Mark J. Adams, Matthew H. Iveson, Archie Campbell, Laurent F. Thomas, Bendik S. Winsvold, Ole Kristian Drange, Sigrid Børte, Abigail R. ter Kuile, Joonas Naamanka, Tan-Hoang Nguyen, Sandra M. Meier, Elizabeth C. Corfield, Laurie Hannigan, Daniel F. Levey, Darina Czamara, Heike Weber, Karmel W. Choi, Giorgio Pistis, Baptiste Couvy-Duchesne, Sandra Van der Auwera, Alexander Teumer, Robert Karlsson, Miguel Garcia-Argibay, Donghyung Lee, Rujia Wang
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat–response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.
{"title":"Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling","authors":"Nora I. Strom, Brad Verhulst, Silviu-Alin Bacanu, Rosa Cheesman, Kirstin L. Purves, Hüseyin Gedik, Brittany L. Mitchell, Alex S. Kwong, Annika B. Faucon, Kritika Singh, Sarah Medland, Lucia Colodro-Conde, Kristi Krebs, Per Hoffmann, Stefan Herms, Jan Gehlen, Stephan Ripke, Swapnil Awasthi, Teemu Palviainen, Elisa M. Tasanko, Roseann E. Peterson, Daniel E. Adkins, Andrey A. Shabalin, Mark J. Adams, Matthew H. Iveson, Archie Campbell, Laurent F. Thomas, Bendik S. Winsvold, Ole Kristian Drange, Sigrid Børte, Abigail R. ter Kuile, Joonas Naamanka, Tan-Hoang Nguyen, Sandra M. Meier, Elizabeth C. Corfield, Laurie Hannigan, Daniel F. Levey, Darina Czamara, Heike Weber, Karmel W. Choi, Giorgio Pistis, Baptiste Couvy-Duchesne, Sandra Van der Auwera, Alexander Teumer, Robert Karlsson, Miguel Garcia-Argibay, Donghyung Lee, Rujia Wang","doi":"10.1038/s41588-025-02485-8","DOIUrl":"https://doi.org/10.1038/s41588-025-02485-8","url":null,"abstract":"The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat–response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"87 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102117","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}
Pub Date : 2026-02-03DOI: 10.1038/s41588-025-02499-2
Elizabeth Cooper, David A. Posner, Colin Y. C. Lee, Linda Hu, Sigourney Bonner, Jessica T. Taylor, Oscar Baldwin, Rocio Jimenez-Guerrero, Katherine E. Masih, Katherine Wickham Rahrmann, Jason Eigenbrood, Gina Ngo, Valar Nila Roamio Franklin, Clive S. D’Santos, Richard Mair, Thomas Santarius, Claudia Craven, Ibrahim Jalloh, Julia Moreno Vicente, Timotheus Y. F. Halim, Li Wang, Arnold R. Kreigstien, Brandon Wainwright, Fredrik J. Swartling, Javed Khan, Menna R. Clatworthy, Richard J. Gilbertson
Recent research has challenged a long-held view of the brain as an immune-privileged organ, revealing active immunosurveillance with therapeutic relevance. Using a new genetically engineered mouse model of ZFTA–RELA ependymoma, a childhood brain tumor, we characterized an immune circuit between the tumor and antigen-presenting hematopoietic stem and progenitor cells (HSPCs) in the skull bone marrow. The presentation of antigens by HSPCs to CD4+ T cells biased HSPC lineages toward myelopoiesis and polarized CD4+ T cells to regulatory T cells, culminating in tumor immunotolerance. Remarkably, normalizing hematopoiesis with a single infusion of antibodies directed against cytokines enriched in the cerebrospinal fluid of mice bearing ZFTA–RELA ependymomas, choroid plexus carcinomas or group 3 medulloblastoma—all aggressive childhood brain tumors—disrupted this process and caused profound tumor regression. These findings demonstrate the existence of a skull bone marrow–tumor immunological interface and suggest that modulating the local supply of myeloid cells could represent a less toxic therapeutic strategy for aggressive childhood brain tumors.
{"title":"Childhood brain tumors instruct cranial hematopoiesis and immunotolerance","authors":"Elizabeth Cooper, David A. Posner, Colin Y. C. Lee, Linda Hu, Sigourney Bonner, Jessica T. Taylor, Oscar Baldwin, Rocio Jimenez-Guerrero, Katherine E. Masih, Katherine Wickham Rahrmann, Jason Eigenbrood, Gina Ngo, Valar Nila Roamio Franklin, Clive S. D’Santos, Richard Mair, Thomas Santarius, Claudia Craven, Ibrahim Jalloh, Julia Moreno Vicente, Timotheus Y. F. Halim, Li Wang, Arnold R. Kreigstien, Brandon Wainwright, Fredrik J. Swartling, Javed Khan, Menna R. Clatworthy, Richard J. Gilbertson","doi":"10.1038/s41588-025-02499-2","DOIUrl":"https://doi.org/10.1038/s41588-025-02499-2","url":null,"abstract":"Recent research has challenged a long-held view of the brain as an immune-privileged organ, revealing active immunosurveillance with therapeutic relevance. Using a new genetically engineered mouse model of ZFTA–RELA ependymoma, a childhood brain tumor, we characterized an immune circuit between the tumor and antigen-presenting hematopoietic stem and progenitor cells (HSPCs) in the skull bone marrow. The presentation of antigens by HSPCs to CD4+ T cells biased HSPC lineages toward myelopoiesis and polarized CD4+ T cells to regulatory T cells, culminating in tumor immunotolerance. Remarkably, normalizing hematopoiesis with a single infusion of antibodies directed against cytokines enriched in the cerebrospinal fluid of mice bearing ZFTA–RELA ependymomas, choroid plexus carcinomas or group 3 medulloblastoma—all aggressive childhood brain tumors—disrupted this process and caused profound tumor regression. These findings demonstrate the existence of a skull bone marrow–tumor immunological interface and suggest that modulating the local supply of myeloid cells could represent a less toxic therapeutic strategy for aggressive childhood brain tumors.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"97 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102118","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}
Pub Date : 2026-02-02DOI: 10.1038/s41588-026-02514-0
{"title":"Single-nucleus DNA sequencing delves into the varied genomic evolution of pancreatic cancer.","authors":"","doi":"10.1038/s41588-026-02514-0","DOIUrl":"https://doi.org/10.1038/s41588-026-02514-0","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106290","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}
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