CellPub Date : 2024-12-06DOI: 10.1016/j.cell.2024.11.002
Svenja K. Tetzlaff, Ekin Reyhan, Nikolas Layer, C. Peter Bengtson, Alina Heuer, Julian Schroers, Anton J. Faymonville, Atefeh Pourkhalili Langeroudi, Nina Drewa, Elijah Keifert, Julia Wagner, Stella J. Soyka, Marc C. Schubert, Nirosan Sivapalan, Rangel L. Pramatarov, Verena Buchert, Tim Wageringel, Elena Grabis, Niklas Wißmann, Obada T. Alhalabi, Varun Venkataramani
{"title":"Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing","authors":"Svenja K. Tetzlaff, Ekin Reyhan, Nikolas Layer, C. Peter Bengtson, Alina Heuer, Julian Schroers, Anton J. Faymonville, Atefeh Pourkhalili Langeroudi, Nina Drewa, Elijah Keifert, Julia Wagner, Stella J. Soyka, Marc C. Schubert, Nirosan Sivapalan, Rangel L. Pramatarov, Verena Buchert, Tim Wageringel, Elena Grabis, Niklas Wißmann, Obada T. Alhalabi, Varun Venkataramani","doi":"10.1016/j.cell.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.002","url":null,"abstract":"Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabies viruses to investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, with cholinergic neurons driving glioblastoma invasion. We uncovered patient-specific and tumor-cell-state-dependent differences in synaptogenic gene expression associated with neuron-tumor connectivity and subsequent invasiveness. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous neuronal activity inhibition and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a viral strategy to tackle glioblastoma. Together, this study provides a framework to comprehensively characterize neuron-tumor networks and target glioblastoma.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"82 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782648","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}
CellPub Date : 2024-12-04DOI: 10.1016/j.cell.2024.11.003
Jazmín Ramos-Madrigal, Gayle J. Fritz, Bryon Schroeder, Bruce Smith, Fátima Sánchez-Barreiro, Christian Carøe, Anne Kathrine Wiborg Runge, Sarah Boer, Krista McGrath, Filipe G. Vieira, Shanlin Liu, Rute R. da Fonseca, Chunxue Guo, Guojie Zhang, Bent Petersen, Thomas Sicheritz-Pontén, Shyam Gopalakrishnan, M. Thomas P. Gilbert, Nathan Wales
{"title":"The genomic origin of early maize in eastern North America","authors":"Jazmín Ramos-Madrigal, Gayle J. Fritz, Bryon Schroeder, Bruce Smith, Fátima Sánchez-Barreiro, Christian Carøe, Anne Kathrine Wiborg Runge, Sarah Boer, Krista McGrath, Filipe G. Vieira, Shanlin Liu, Rute R. da Fonseca, Chunxue Guo, Guojie Zhang, Bent Petersen, Thomas Sicheritz-Pontén, Shyam Gopalakrishnan, M. Thomas P. Gilbert, Nathan Wales","doi":"10.1016/j.cell.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.003","url":null,"abstract":"Indigenous maize varieties from eastern North America have played an outsized role in breeding programs, yet their early origins are not fully understood. We generated paleogenomic data to reconstruct how maize first reached this region and how it was selected during the process. Genomic ancestry analyses reveal recurrent movements northward from different parts of Mexico, likely culminating in at least two dispersals from the US Southwest across the Great Plains to the Ozarks and beyond. We find that 1,000-year-old Ozark specimens carry a highly differentiated <em>wx1</em> gene, which is involved in the synthesis of amylose, highlighting repeated selective pressures on the starch metabolic pathway throughout maize’s domestication. This population shows a close affinity with the lineage that ultimately became the Northern Flints, a major contributor to modern commercial maize.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"26 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763141","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}
CellPub Date : 2024-12-03DOI: 10.1016/j.cell.2024.11.001
Hye Jin Kang, Brian E. Krumm, Adrien Tassou, Matan Geron, Jeffrey F. DiBerto, Nicholas J. Kapolka, Ryan H. Gumpper, Kensuke Sakamoto, D. Dewran Kocak, Reid H.J. Olsen, Xi-Ping Huang, Shicheng Zhang, Karen L. Huang, Saheem A. Zaidi, MyV.T. Nguyen, Min Jeong Jo, Vsevolod Katritch, Jonathan F. Fay, Grégory Scherrer, Bryan L. Roth
{"title":"Structure-guided design of a peripherally restricted chemogenetic system","authors":"Hye Jin Kang, Brian E. Krumm, Adrien Tassou, Matan Geron, Jeffrey F. DiBerto, Nicholas J. Kapolka, Ryan H. Gumpper, Kensuke Sakamoto, D. Dewran Kocak, Reid H.J. Olsen, Xi-Ping Huang, Shicheng Zhang, Karen L. Huang, Saheem A. Zaidi, MyV.T. Nguyen, Min Jeong Jo, Vsevolod Katritch, Jonathan F. Fay, Grégory Scherrer, Bryan L. Roth","doi":"10.1016/j.cell.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.001","url":null,"abstract":"Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remotely controlling cellular signaling, neural activity, behavior, and physiology. Using a structure-guided approach, we provide a peripherally restricted Gi-DREADD, hydroxycarboxylic acid receptor DREADD (HCAD), whose native receptor is minimally expressed in the brain, and a chemical actuator that does not cross the blood-brain barrier (BBB). This was accomplished by combined mutagenesis, analoging via an ultra-large make-on-demand library, structural determination of the designed DREADD receptor via cryoelectron microscopy (cryo-EM), and validation of HCAD function. Expression and activation of HCAD in dorsal root ganglion (DRG) neurons inhibit action potential (AP) firing and reduce both acute and tissue-injury-induced inflammatory pain. The HCAD chemogenetic system expands the possibilities for studying numerous peripheral systems with little adverse effects on the central nervous system (CNS). The structure-guided approach used to generate HCAD also has the potential to accelerate the development of emerging chemogenetic tools for basic and translational sciences.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"13 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760177","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}
CellPub Date : 2024-12-02DOI: 10.1016/j.cell.2024.10.044
Amanda Andersson-Rolf, Kelvin Groot, Jeroen Korving, Harry Begthel, Maaike A.J. Hanegraaf, Michael VanInsberghe, Fredrik Salmén, Stieneke van den Brink, Carmen Lopez-Iglesias, Peter J. Peters, Daniel Krueger, Joep Beumer, Maarten H. Geurts, Anna Alemany, Helmuth Gehart, Françoise Carlotti, Eelco J.P. de Koning, Susana M. Chuva de Sousa Lopes, Alexander van Oudenaarden, Johan H. van Es, Hans Clevers
{"title":"Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages","authors":"Amanda Andersson-Rolf, Kelvin Groot, Jeroen Korving, Harry Begthel, Maaike A.J. Hanegraaf, Michael VanInsberghe, Fredrik Salmén, Stieneke van den Brink, Carmen Lopez-Iglesias, Peter J. Peters, Daniel Krueger, Joep Beumer, Maarten H. Geurts, Anna Alemany, Helmuth Gehart, Françoise Carlotti, Eelco J.P. de Koning, Susana M. Chuva de Sousa Lopes, Alexander van Oudenaarden, Johan H. van Es, Hans Clevers","doi":"10.1016/j.cell.2024.10.044","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.044","url":null,"abstract":"The mammalian pancreas consists of three epithelial compartments: the acini and ducts of the exocrine pancreas and the endocrine islets of Langerhans. Murine studies indicate that these three compartments derive from a transient, common pancreatic progenitor. Here, we report derivation of 18 human fetal pancreas organoid (hfPO) lines from gestational weeks 8–17 (8–17 GWs) fetal pancreas samples. Four of these lines, derived from 15 to 16 GWs samples, generate acinar-, ductal-, and endocrine-lineage cells while expanding exponentially for >2 years under optimized culture conditions. Single-cell RNA sequencing identifies rare LGR5<sup>+</sup> cells in fetal pancreas and in hfPOs as the root of the developmental hierarchy. These LGR5<sup>+</sup> cells share multiple markers with adult gastrointestinal tract stem cells. Organoids derived from single LGR5<sup>+</sup> organoid-derived cells recapitulate this tripotency <em>in vitro</em>. We describe a human fetal tripotent stem/progenitor cell capable of long-term expansion <em>in vitro</em> and of generating all three pancreatic cell lineages.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"18 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760542","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}
CellPub Date : 2024-11-27DOI: 10.1016/j.cell.2024.10.051
Alessandra Dall’Agnese, Ming M. Zheng, Shannon Moreno, Jesse M. Platt, An T. Hoang, Deepti Kannan, Giuseppe Dall’Agnese, Kalon J. Overholt, Ido Sagi, Nancy M. Hannett, Hailey Erb, Olivia Corradin, Arup K. Chakraborty, Tong Ihn Lee, Richard A. Young
{"title":"Proteolethargy is a pathogenic mechanism in chronic disease","authors":"Alessandra Dall’Agnese, Ming M. Zheng, Shannon Moreno, Jesse M. Platt, An T. Hoang, Deepti Kannan, Giuseppe Dall’Agnese, Kalon J. Overholt, Ido Sagi, Nancy M. Hannett, Hailey Erb, Olivia Corradin, Arup K. Chakraborty, Tong Ihn Lee, Richard A. Young","doi":"10.1016/j.cell.2024.10.051","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.051","url":null,"abstract":"The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718783","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}
CellPub Date : 2024-11-26DOI: 10.1016/j.cell.2024.11.023
María Ramos Zapatero, Alexander Tong, James W. Opzoomer, Rhianna O’Sullivan, Ferran Cardoso Rodriguez, Jahangir Sufi, Petra Vlckova, Callum Nattress, Xiao Qin, Jeroen Claus, Daniel Hochhauser, Smita Krishnaswamy, Christopher J. Tape
{"title":"Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses","authors":"María Ramos Zapatero, Alexander Tong, James W. Opzoomer, Rhianna O’Sullivan, Ferran Cardoso Rodriguez, Jahangir Sufi, Petra Vlckova, Callum Nattress, Xiao Qin, Jeroen Claus, Daniel Hochhauser, Smita Krishnaswamy, Christopher J. Tape","doi":"10.1016/j.cell.2024.11.023","DOIUrl":"https://doi.org/10.1016/j.cell.2024.11.023","url":null,"abstract":"(Cell <em>186</em>, 5606–5619.e1–e24; December 7, 2023)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"23 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718567","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}
CellPub Date : 2024-11-25DOI: 10.1016/j.cell.2024.10.047
Yuqi Wang, Mangze Hu, Jian Cao, Fengxiang Wang, Jingrong Regina Han, Tianshu William Wu, Luxiao Li, Jinshi Yu, Yujing Fan, Guanglei Xie, Heyuan Lian, Yueying Cao, Nathchar Naowarojna, Xi Wang, Yilong Zou
{"title":"ACSL4 and polyunsaturated lipids support metastatic extravasation and colonization","authors":"Yuqi Wang, Mangze Hu, Jian Cao, Fengxiang Wang, Jingrong Regina Han, Tianshu William Wu, Luxiao Li, Jinshi Yu, Yujing Fan, Guanglei Xie, Heyuan Lian, Yueying Cao, Nathchar Naowarojna, Xi Wang, Yilong Zou","doi":"10.1016/j.cell.2024.10.047","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.047","url":null,"abstract":"Metastatic dissemination to distant organs demands that cancer cells possess high morphological and metabolic adaptability. However, contributions of the cellular lipidome to metastasis remain elusive. Here, we uncover a correlation between metastasis potential and ferroptosis susceptibility in multiple cancers. Metastases-derived cancer cells exhibited higher ferroptosis sensitivity and polyunsaturated fatty acyl (PUFA)-lipid contents than primary-tumor-derived cells from ovarian cancer patients. Metabolism-focused CRISPR screens in a mouse model for ovarian cancer distant metastasis established via two rounds of <em>in vivo</em> selection revealed the PUFA-lipid biosynthesis enzyme acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) as a pro-hematogenous metastasis factor. ACSL4 promotes metastatic extravasation by enhancing membrane fluidity and cellular invasiveness. While promoting metastasis, the high PUFA-lipid state creates dependencies on abhydrolase-domain-containing 6, acylglycerol lipase (ABHD6), enoyl-CoA delta isomerase 1 (ECI1), and enoyl-CoA hydratase 1 (ECH1)—rate-limiting enzymes preparing unsaturated fatty acids (UFAs) for β-oxidation. ACSL4/ECH1 co-inhibition achieved potent suppression of metastasis. Our work establishes the dual functions of PUFA-lipids in tumor progression and metastasis that may be exploitable for therapeutic development.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"238 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696577","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}
CellPub Date : 2024-11-25DOI: 10.1016/j.cell.2024.10.048
Stephanie Torrino, William M. Oldham, Andrés R. Tejedor, Ignacio S. Burgos, Lara Nasr, Nesrine Rachedi, Kéren Fraissard, Caroline Chauvet, Chaima Sbai, Brendan P. O’Hara, Sophie Abélanet, Frederic Brau, Cyril Favard, Stephan Clavel, Rosana Collepardo-Guevara, Jorge R. Espinosa, Issam Ben-Sahra, Thomas Bertero
{"title":"Mechano-dependent sorbitol accumulation supports biomolecular condensate","authors":"Stephanie Torrino, William M. Oldham, Andrés R. Tejedor, Ignacio S. Burgos, Lara Nasr, Nesrine Rachedi, Kéren Fraissard, Caroline Chauvet, Chaima Sbai, Brendan P. O’Hara, Sophie Abélanet, Frederic Brau, Cyril Favard, Stephan Clavel, Rosana Collepardo-Guevara, Jorge R. Espinosa, Issam Ben-Sahra, Thomas Bertero","doi":"10.1016/j.cell.2024.10.048","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.048","url":null,"abstract":"Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation <em>in vivo</em>. We demonstrate that the extracellular matrix links mechanical cues with the control of glucose metabolism to sorbitol. In turn, sorbitol acts as a natural crowding agent to promote biomolecular condensation. Using <em>in silico</em> simulations and <em>in vitro</em> assays, we establish that variations in the physiological range of sorbitol concentrations, but not glucose concentrations, are sufficient to regulate biomolecular condensates. Accordingly, pharmacological and genetic manipulation of intracellular sorbitol concentration modulates biomolecular condensates in breast cancer—a mechano-dependent disease. We propose that sorbitol is a mechanosensitive metabolite enabling protein condensation to control mechano-regulated cellular functions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"2 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696576","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}
CellPub Date : 2024-11-22DOI: 10.1016/j.cell.2024.10.046
Bei Liu, Tong Wu, Bernadette A. Miao, Fei Ji, Shun Liu, Pingluan Wang, Yutao Zhao, Yuhao Zhong, Arunkumar Sundaram, Tie-Bo Zeng, Marta Majcherska-Agrawal, Robert J. Keenan, Tao Pan, Chuan He
{"title":"snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification","authors":"Bei Liu, Tong Wu, Bernadette A. Miao, Fei Ji, Shun Liu, Pingluan Wang, Yutao Zhao, Yuhao Zhong, Arunkumar Sundaram, Tie-Bo Zeng, Marta Majcherska-Agrawal, Robert J. Keenan, Tao Pan, Chuan He","doi":"10.1016/j.cell.2024.10.046","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.046","url":null,"abstract":"Small nucleolar RNAs (snoRNAs) are non-coding RNAs known for guiding RNA modifications, including 2′-<em>O</em>-methylation (N<sub>m</sub>) and pseudouridine (Ψ). While snoRNAs may also interact with other RNAs, such as mRNA, the full repertoire of RNAs targeted by snoRNA remains elusive due to the lack of effective technologies that identify snoRNA targets transcriptome wide. Here, we develop a chemical crosslinking-based approach that comprehensively detects cellular RNA targets of snoRNAs, yielding thousands of previously unrecognized snoRNA-mRNA interactions in human cells and mouse brain tissues. Many interactions occur outside of snoRNA-guided RNA modification sites, hinting at non-canonical functions beyond RNA modification. We find that one of these snoRNAs, <em>SNORA73</em>, targets mRNAs that encode secretory proteins and membrane proteins. <em>SNORA73</em> also interacts with <em>7SL</em> RNA, part of the signal recognition particle (SRP) required for protein secretion. The mRNA-<em>SNORA73</em>-<em>7SL</em> RNA interactions enhance the association of the <em>SNORA73</em>-target mRNAs with SRP, thereby facilitating the secretion of encoded proteins.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"234 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684947","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}
{"title":"Atlas of the plasma proteome in health and disease in 53,026 adults","authors":"Yue-Ting Deng, Jia You, Yu He, Yi Zhang, Hai-Yun Li, Xin-Rui Wu, Ji-Yun Cheng, Yu Guo, Zi-Wen Long, Yi-Lin Chen, Ze-Yu Li, Liu Yang, Ya-Ru Zhang, Shi-Dong Chen, Yi-Jun Ge, Yu-Yuan Huang, Le-Ming Shi, Qiang Dong, Ying Mao, Jian-Feng Feng, Jin-Tai Yu","doi":"10.1016/j.cell.2024.10.045","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.045","url":null,"abstract":"Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine. Here, we provide a detailed atlas of 2,920 plasma proteins linking to diseases (406 prevalent and 660 incident) and 986 health-related traits in 53,026 individuals (median follow-up: 14.8 years) from the UK Biobank, representing the most comprehensive proteome profiles to date. This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations. Over 650 proteins were shared among at least 50 diseases, and over 1,000 showed sex and age heterogeneity. Furthermore, proteins demonstrated promising potential in disease discrimination (area under the curve [AUC] > 0.80 in 183 diseases). Finally, integrating protein quantitative trait locus data determined 474 causal proteins, providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles. These results provide an open-access comprehensive proteome-phenome resource (<span><span>https://proteome-phenome-atlas.com/</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>) to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers, prediction models, and therapeutic targets.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"188 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684948","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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