Pub Date : 2025-01-23DOI: 10.1016/j.cell.2025.01.004
Ming Zhang, Juan Feng, Chun Xie, Nan Song, Chaozhi Jin, Jian Wang, Qun Zhao, Lihua Zhang, Boshuang Wang, Yidi Sun, Fei Guo, Yang Li, Shujia Zhu
The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs in vivo.
{"title":"Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus","authors":"Ming Zhang, Juan Feng, Chun Xie, Nan Song, Chaozhi Jin, Jian Wang, Qun Zhao, Lihua Zhang, Boshuang Wang, Yidi Sun, Fei Guo, Yang Li, Shujia Zhu","doi":"10.1016/j.cell.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.cell.2025.01.004","url":null,"abstract":"The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving <em>N</em>-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus. Three major subtypes of GluN1-N2A-N2B, GluN1-N2B, and GluN1-N2A eNMDARs were resolved by cryoelectron microscopy (cryo-EM) at the resolution up to 4.2 Å. The particle ratio of these three subtypes was 9:7:4, indicating that about half of GluN2A and GluN2B subunits are incorporated into the tri-heterotetramers. Structural analysis revealed the asymmetric architecture of the GluN1-N2A-N2B receptor throughout the extracellular to the transmembrane layers. Moreover, the conformational variations between GluN1-N2B and GluN1-N2A-N2B receptors revealed the distinct biophysical properties across different eNMDAR subtypes. Our findings imply the structural and functional complexity of eNMDARs and shed light on structure-based therapeutic design targeting these eNMDARs <em>in vivo</em>.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"33 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020983","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 : 2025-01-23DOI: 10.1016/j.cell.2024.12.024
Xinhang Tan, Dapeng Wang, Xiaowei Zhang, Shuang Zheng, Xiaojie Jia, Hui Liu, Zilin Liu, Hao Yang, Huiling Dai, Xi Chen, Zhixin Qian, Ran Wang, Miaolian Ma, Peng Zhang, Nan Yu, Ertao Wang
Most land plants form symbioses with microbes to acquire nutrients but also must restrict infection by pathogens. Here, we show that a single pair of lysin-motif-containing receptor-like kinases, MpaLYR and MpaCERK1, mediates both immunity and symbiosis in the liverwort Marchantia paleacea. MpaLYR has a higher affinity for long-chain (CO7) versus short-chain chitin oligomers (CO4). Although both CO7 and CO4 can activate symbiosis-related genes, CO7 triggers stronger immune responses than CO4 in a dosage-dependent manner. CO4 can inhibit CO7-induced strong immune responses, recapitulating the early response to inoculation with the symbiont arbuscular mycorrhizal fungi. We show that phosphate starvation of plants increases their production of strigolactone, which stimulates CO4/CO5 secretion from mycorrhizal fungi, thereby prioritizing symbiosis over immunity. Thus, a single pair of LysM receptors mediates dosage-dependent perception of different chitin oligomers to discern symbiotic and pathogenic microbes in M. paleacea, which may facilitate terrestrialization.
{"title":"A pair of LysM receptors mediates symbiosis and immunity discrimination in Marchantia","authors":"Xinhang Tan, Dapeng Wang, Xiaowei Zhang, Shuang Zheng, Xiaojie Jia, Hui Liu, Zilin Liu, Hao Yang, Huiling Dai, Xi Chen, Zhixin Qian, Ran Wang, Miaolian Ma, Peng Zhang, Nan Yu, Ertao Wang","doi":"10.1016/j.cell.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.024","url":null,"abstract":"Most land plants form symbioses with microbes to acquire nutrients but also must restrict infection by pathogens. Here, we show that a single pair of lysin-motif-containing receptor-like kinases, MpaLYR and MpaCERK1, mediates both immunity and symbiosis in the liverwort <em>Marchantia paleacea</em>. MpaLYR has a higher affinity for long-chain (CO7) versus short-chain chitin oligomers (CO4). Although both CO7 and CO4 can activate symbiosis-related genes, CO7 triggers stronger immune responses than CO4 in a dosage-dependent manner. CO4 can inhibit CO7-induced strong immune responses, recapitulating the early response to inoculation with the symbiont arbuscular mycorrhizal fungi. We show that phosphate starvation of plants increases their production of strigolactone, which stimulates CO4/CO5 secretion from mycorrhizal fungi, thereby prioritizing symbiosis over immunity. Thus, a single pair of LysM receptors mediates dosage-dependent perception of different chitin oligomers to discern symbiotic and pathogenic microbes in <em>M. paleacea</em>, which may facilitate terrestrialization.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"52 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021104","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 : 2025-01-23DOI: 10.1016/j.cell.2024.12.026
Section snippets
Main text
As we wrap up our year-long celebration of Cell’s 50th anniversary, we present “Cell Line: 2014–2024,” a Timeline highlighting a set of exceptional scientific works—both landmark papers and essential reviews—published in the journal. This fifth installment rounds out the five decades since Cell’s launch in 1974. Previous Cell Lines covered the decades since the journal’s inception: 1974–1983, 1984–1993, 1994–2003, and 2004–2014. Among the landmark papers featured are 26 Nobel Prize-winning
{"title":"Cell Line: 2014–2024","authors":"","doi":"10.1016/j.cell.2024.12.026","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.026","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>As we wrap up our year-long celebration of <em>Cell</em>’s 50<sup>th</sup> anniversary, we present “Cell Line: 2014–2024,” a Timeline highlighting a set of exceptional scientific works—both landmark papers and essential reviews—published in the journal. This fifth installment rounds out the five decades since <em>Cell</em>’s launch in 1974. Previous Cell Lines covered the decades since the journal’s inception: <span><span>1974–1983</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>1984–1993</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>1994–2003</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and <span><span>2004–2014</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. Among the landmark papers featured are 26 Nobel Prize-winning</section></section>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"15 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021107","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}
Despite recent advances in imaging- and antibody-based methods, achieving in-depth, high-resolution protein mapping across entire tissues remains a significant challenge in spatial proteomics. Here, we present parallel-flow projection and transfer learning across omics data (PLATO), an integrated framework combining microfluidics with deep learning to enable high-resolution mapping of thousands of proteins in whole tissue sections. We validated the PLATO framework by profiling the spatial proteome of the mouse cerebellum, identifying 2,564 protein groups in a single run. We then applied PLATO to rat villus and human breast cancer samples, achieving a spatial resolution of 25 μm and uncovering proteomic dynamics associated with disease states. This approach revealed spatially distinct tumor subtypes, identified key dysregulated proteins, and provided novel insights into the complexity of the tumor microenvironment. We believe that PLATO represents a transformative platform for exploring spatial proteomic regulation and its interplay with genetic and environmental factors.
{"title":"High-resolution spatially resolved proteomics of complex tissues based on microfluidics and transfer learning","authors":"Beiyu Hu, Ruiqiao He, Kun Pang, Guibin Wang, Ning Wang, Wenzhuo Zhu, Xin Sui, Huajing Teng, Tianxin Liu, Junjie Zhu, Zewen Jiang, Jinyang Zhang, Zhenqiang Zuo, Weihu Wang, Peifeng Ji, Fangqing Zhao","doi":"10.1016/j.cell.2024.12.023","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.023","url":null,"abstract":"Despite recent advances in imaging- and antibody-based methods, achieving in-depth, high-resolution protein mapping across entire tissues remains a significant challenge in spatial proteomics. Here, we present parallel-flow projection and transfer learning across omics data (PLATO), an integrated framework combining microfluidics with deep learning to enable high-resolution mapping of thousands of proteins in whole tissue sections. We validated the PLATO framework by profiling the spatial proteome of the mouse cerebellum, identifying 2,564 protein groups in a single run. We then applied PLATO to rat villus and human breast cancer samples, achieving a spatial resolution of 25 μm and uncovering proteomic dynamics associated with disease states. This approach revealed spatially distinct tumor subtypes, identified key dysregulated proteins, and provided novel insights into the complexity of the tumor microenvironment. We believe that PLATO represents a transformative platform for exploring spatial proteomic regulation and its interplay with genetic and environmental factors.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"12 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020981","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 : 2025-01-23DOI: 10.1016/j.cell.2024.12.025
Kathryn Kixmoeller, Ekaterina V. Tarasovetc, Elie Mer, Yi-Wei Chang, Ben E. Black
The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing. We find that CENP-C is required in mitosis, not just for kinetochore assembly, likely reflecting its role in organizing the inner kinetochore during chromosome segregation. We further visualize the scaffold of the fibrous corona, a structure amplified at unattached kinetochores, revealing crescent-shaped parallel arrays of fibrils extending >1 μm. Thus, we reveal how the organization of centromeric chromatin creates a clearing at the site of kinetochore formation as well as the nature of kinetochore amplification mediated by corona fibrils.
{"title":"Centromeric chromatin clearings demarcate the site of kinetochore formation","authors":"Kathryn Kixmoeller, Ekaterina V. Tarasovetc, Elie Mer, Yi-Wei Chang, Ben E. Black","doi":"10.1016/j.cell.2024.12.025","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.025","url":null,"abstract":"The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing. We find that CENP-C is required in mitosis, not just for kinetochore assembly, likely reflecting its role in organizing the inner kinetochore during chromosome segregation. We further visualize the scaffold of the fibrous corona, a structure amplified at unattached kinetochores, revealing crescent-shaped parallel arrays of fibrils extending >1 μm. Thus, we reveal how the organization of centromeric chromatin creates a clearing at the site of kinetochore formation as well as the nature of kinetochore amplification mediated by corona fibrils.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"4 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020986","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 : 2025-01-23DOI: 10.1016/j.cell.2024.12.034
Fuyong Li, Anissa M. Armet, Katri Korpela, Junhong Liu, Rodrigo Margain Quevedo, Francesco Asnicar, Benjamin Seethaler, Tianna B.S. Rusnak, Janis L. Cole, Zhihong Zhang, Shuang Zhao, Xiaohang Wang, Adele Gagnon, Edward C. Deehan, João F. Mota, Jeffrey A. Bakal, Russell Greiner, Dan Knights, Nicola Segata, Stephan C. Bischoff, Jens Walter
Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of L. reuteri strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The diet also beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable cardiometabolic benefits were observed independently of L. reuteri administration, several of which could be accurately predicted by baseline and diet-responsive microbiome features. The findings suggest that a dietary intervention targeted toward restoring the gut microbiome can improve host-microbiome interactions that likely underpin chronic pathologies, which can guide dietary recommendations and the development of therapeutic and nutritional strategies.
{"title":"Cardiometabolic benefits of a non-industrialized-type diet are linked to gut microbiome modulation","authors":"Fuyong Li, Anissa M. Armet, Katri Korpela, Junhong Liu, Rodrigo Margain Quevedo, Francesco Asnicar, Benjamin Seethaler, Tianna B.S. Rusnak, Janis L. Cole, Zhihong Zhang, Shuang Zhao, Xiaohang Wang, Adele Gagnon, Edward C. Deehan, João F. Mota, Jeffrey A. Bakal, Russell Greiner, Dan Knights, Nicola Segata, Stephan C. Bischoff, Jens Walter","doi":"10.1016/j.cell.2024.12.034","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.034","url":null,"abstract":"Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (<em>Limosilactobacillus reuteri</em>) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of <em>L. reuteri</em> strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The diet also beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable cardiometabolic benefits were observed independently of <em>L. reuteri</em> administration, several of which could be accurately predicted by baseline and diet-responsive microbiome features. The findings suggest that a dietary intervention targeted toward restoring the gut microbiome can improve host-microbiome interactions that likely underpin chronic pathologies, which can guide dietary recommendations and the development of therapeutic and nutritional strategies.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"22 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021062","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 : 2025-01-22DOI: 10.1016/j.cell.2024.12.022
Sool Lee, Jessica C. McAfee, Jiseok Lee, Alejandro Gomez, Austin T. Ledford, Declan Clarke, Hyunggyu Min, Mark B. Gerstein, Alan P. Boyle, Patrick F. Sullivan, Adriana S. Beltran, Hyejung Won
A meta-genome-wide association study across eight psychiatric disorders has highlighted the genetic architecture of pleiotropy in major psychiatric disorders. However, mechanisms underlying pleiotropic effects of the associated variants remain to be explored. We conducted a massively parallel reporter assay to decode the regulatory logic of variants with pleiotropic and disorder-specific effects. Pleiotropic variants differ from disorder-specific variants by exhibiting chromatin accessibility that extends across diverse cell types in the neuronal lineage and by altering motifs for transcription factors with higher connectivity in protein-protein interaction networks. We mapped pleiotropic and disorder-specific variants to putative target genes using functional genomics approaches and CRISPR perturbation. In vivo CRISPR perturbation of a pleiotropic and a disorder-specific gene suggests that pleiotropy may involve the regulation of genes expressed broadly across neuronal cell types and with higher network connectivity.
{"title":"Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders","authors":"Sool Lee, Jessica C. McAfee, Jiseok Lee, Alejandro Gomez, Austin T. Ledford, Declan Clarke, Hyunggyu Min, Mark B. Gerstein, Alan P. Boyle, Patrick F. Sullivan, Adriana S. Beltran, Hyejung Won","doi":"10.1016/j.cell.2024.12.022","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.022","url":null,"abstract":"A meta-genome-wide association study across eight psychiatric disorders has highlighted the genetic architecture of pleiotropy in major psychiatric disorders. However, mechanisms underlying pleiotropic effects of the associated variants remain to be explored. We conducted a massively parallel reporter assay to decode the regulatory logic of variants with pleiotropic and disorder-specific effects. Pleiotropic variants differ from disorder-specific variants by exhibiting chromatin accessibility that extends across diverse cell types in the neuronal lineage and by altering motifs for transcription factors with higher connectivity in protein-protein interaction networks. We mapped pleiotropic and disorder-specific variants to putative target genes using functional genomics approaches and CRISPR perturbation. <em>In vivo</em> CRISPR perturbation of a pleiotropic and a disorder-specific gene suggests that pleiotropy may involve the regulation of genes expressed broadly across neuronal cell types and with higher network connectivity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"24 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991911","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 : 2025-01-22DOI: 10.1016/j.cell.2024.12.017
Richard J. Abdill, Samantha P. Graham, Vincent Rubinetti, Mansooreh Ahmadian, Parker Hicks, Ashwin Chetty, Daniel McDonald, Pamela Ferretti, Elizabeth Gibbons, Marco Rossi, Arjun Krishnan, Frank W. Albert, Casey S. Greene, Sean Davis, Ran Blekhman
The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline. We use this compendium to evaluate geographic and technical effects on microbiome variation. We find that regions such as Central and Southern Asia differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America and that composition alone can be used to predict a sample’s region of origin. We also find strong associations between microbiome variation and technical factors such as primers and DNA extraction. We anticipate this growing work, the Human Microbiome Compendium, will enable advanced applied and methodological research.
{"title":"Integration of 168,000 samples reveals global patterns of the human gut microbiome","authors":"Richard J. Abdill, Samantha P. Graham, Vincent Rubinetti, Mansooreh Ahmadian, Parker Hicks, Ashwin Chetty, Daniel McDonald, Pamela Ferretti, Elizabeth Gibbons, Marco Rossi, Arjun Krishnan, Frank W. Albert, Casey S. Greene, Sean Davis, Ran Blekhman","doi":"10.1016/j.cell.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.017","url":null,"abstract":"The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline. We use this compendium to evaluate geographic and technical effects on microbiome variation. We find that regions such as Central and Southern Asia differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America and that composition alone can be used to predict a sample’s region of origin. We also find strong associations between microbiome variation and technical factors such as primers and DNA extraction. We anticipate this growing work, the Human Microbiome Compendium, will enable advanced applied and methodological research.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"25 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991910","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 : 2025-01-21DOI: 10.1016/j.cell.2024.12.018
Rong Zeng, Yiting Shi, Li Guo, Diyi Fu, Minze Li, Xiaoyan Zhang, Zhuoyang Li, Junhong Zhuang, Xiaohong Yang, Jianru Zuo, Zhizhong Gong, Feng Tian, Shuhua Yang
Low temperature severely limits the growth, yield, and geographical distribution of maize (Zea mays L.). How maize adapts to cold climates remains largely unclear. Here, we identify a basic helix-loop-helix (bHLH) transcription factor, COLD-RESPONSIVE OPERATION LOCUS 1 (COOL1), as a crucial regulator of maize cold tolerance through genome-wide association studies. Natural variations in the COOL1 promoter affect the binding affinity of ELONGATED HYPOCOTYL5 (HY5), a transcriptional factor repressing COOL1 transcription. COOL1, in turn, negatively regulates downstream cold-responsive genes, thereby modulating cold tolerance. Moreover, calcium-dependent protein kinase CPK17 translocates to the nucleus and stabilizes COOL1 in response to cold stress. Intriguingly, the cold-tolerant allele of COOL1 is predominantly distributed in northern high latitudes with cold climates. This study defines a previously unknown pathway by which the COOL1-centered module regulates cold tolerance for high latitudinal adaptation in maize.
低温严重限制了玉米（Zea mays L.）的生长、产量和地理分布。玉米如何适应寒冷气候在很大程度上仍不清楚。在此，我们通过全基因组关联研究确定了一个基本的螺旋-环-螺旋（bHLH）转录因子，cold - responsive OPERATION LOCUS 1 (COOL1)，作为玉米耐寒性的关键调控因子。COOL1启动子的自然变异影响了抑制COOL1转录的转录因子伸长下cotyl5 （HY5）的结合亲和力。COOL1反过来负向调节下游冷反应基因，从而调节耐寒性。此外，钙依赖性蛋白激酶CPK17在冷胁迫下易位到细胞核并稳定COOL1。有趣的是，COOL1的耐寒等位基因主要分布在气候寒冷的北方高纬度地区。这项研究确定了一个以前未知的途径，通过该途径，以cool1为中心的模块调节玉米的耐冷性以适应高纬度环境。
{"title":"A natural variant of COOL1 gene enhances cold tolerance for high-latitude adaptation in maize","authors":"Rong Zeng, Yiting Shi, Li Guo, Diyi Fu, Minze Li, Xiaoyan Zhang, Zhuoyang Li, Junhong Zhuang, Xiaohong Yang, Jianru Zuo, Zhizhong Gong, Feng Tian, Shuhua Yang","doi":"10.1016/j.cell.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.018","url":null,"abstract":"Low temperature severely limits the growth, yield, and geographical distribution of maize (<em>Zea mays</em> L.). How maize adapts to cold climates remains largely unclear. Here, we identify a basic helix-loop-helix (bHLH) transcription factor, COLD-RESPONSIVE OPERATION LOCUS 1 (COOL1), as a crucial regulator of maize cold tolerance through genome-wide association studies. Natural variations in the <em>COOL1</em> promoter affect the binding affinity of ELONGATED HYPOCOTYL5 (HY5), a transcriptional factor repressing <em>COOL1</em> transcription. COOL1, in turn, negatively regulates downstream cold-responsive genes, thereby modulating cold tolerance. Moreover, calcium-dependent protein kinase CPK17 translocates to the nucleus and stabilizes COOL1 in response to cold stress. Intriguingly, the cold-tolerant allele of <em>COOL1</em> is predominantly distributed in northern high latitudes with cold climates. This study defines a previously unknown pathway by which the COOL1-centered module regulates cold tolerance for high latitudinal adaptation in maize.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"74 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991914","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 : 2025-01-21DOI: 10.1016/j.cell.2024.12.019
Tara I. McIntyre, Omar Valdez, Nathan P. Kochhar, Brittany Davidson, Bushra Samad, Longhui Qiu, Kenneth Hu, Alexis J. Combes, Adrian Erlebacher
Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy. By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy. Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3. This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation. This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor.
{"title":"KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice","authors":"Tara I. McIntyre, Omar Valdez, Nathan P. Kochhar, Brittany Davidson, Bushra Samad, Longhui Qiu, Kenneth Hu, Alexis J. Combes, Adrian Erlebacher","doi":"10.1016/j.cell.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.cell.2024.12.019","url":null,"abstract":"Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy. By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy. Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3. This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation. This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"25 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990655","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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