CellPub Date : 2024-02-29DOI: 10.1016/j.cell.2024.01.038
Tom van der Valk, Love Dalèn
{"title":"From genomic threat assessment to conservation action.","authors":"Tom van der Valk, Love Dalèn","doi":"10.1016/j.cell.2024.01.038","DOIUrl":"10.1016/j.cell.2024.01.038","url":null,"abstract":"<p><p>Genomic approaches have the potential to play a pivotal role in conservation, both to detect threats to species and populations and to restore biodiversity through actions. We here separate these approaches into two subdisciplines, vulnerability and restoration genomics, and discuss current applications, outstanding questions, and future potential.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1038-1041"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012237","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.049
Jae-Hyun Yang, Motoshi Hayano, Patrick T Griffin, João A Amorim, Michael S Bonkowski, John K Apostolides, Elias L Salfati, Marco Blanchette, Elizabeth M Munding, Mital Bhakta, Yap Ching Chew, Wei Guo, Xiaojing Yang, Sun Maybury-Lewis, Xiao Tian, Jaime M Ross, Giuseppe Coppotelli, Margarita V Meer, Ryan Rogers-Hammond, Daniel L Vera, Yuancheng Ryan Lu, Jeffrey W Pippin, Michael L Creswell, Zhixun Dou, Caiyue Xu, Sarah J Mitchell, Abhirup Das, Brendan L O'Connell, Sachin Thakur, Alice E Kane, Qiao Su, Yasuaki Mohri, Emi K Nishimura, Laura Schaevitz, Neha Garg, Ana-Maria Balta, Meghan A Rego, Meredith Gregory-Ksander, Tatjana C Jakobs, Lei Zhong, Hiroko Wakimoto, Jihad El Andari, Dirk Grimm, Raul Mostoslavsky, Amy J Wagers, Kazuo Tsubota, Stephen J Bonasera, Carlos M Palmeira, Jonathan G Seidman, Christine E Seidman, Norman S Wolf, Jill A Kreiling, John M Sedivy, George F Murphy, Richard E Green, Benjamin A Garcia, Shelley L Berger, Philipp Oberdoerffer, Stuart J Shankland, Vadim N Gladyshev, Bruce R Ksander, Andreas R Pfenning, Luis A Rajman, David A Sinclair
{"title":"Loss of epigenetic information as a cause of mammalian aging.","authors":"Jae-Hyun Yang, Motoshi Hayano, Patrick T Griffin, João A Amorim, Michael S Bonkowski, John K Apostolides, Elias L Salfati, Marco Blanchette, Elizabeth M Munding, Mital Bhakta, Yap Ching Chew, Wei Guo, Xiaojing Yang, Sun Maybury-Lewis, Xiao Tian, Jaime M Ross, Giuseppe Coppotelli, Margarita V Meer, Ryan Rogers-Hammond, Daniel L Vera, Yuancheng Ryan Lu, Jeffrey W Pippin, Michael L Creswell, Zhixun Dou, Caiyue Xu, Sarah J Mitchell, Abhirup Das, Brendan L O'Connell, Sachin Thakur, Alice E Kane, Qiao Su, Yasuaki Mohri, Emi K Nishimura, Laura Schaevitz, Neha Garg, Ana-Maria Balta, Meghan A Rego, Meredith Gregory-Ksander, Tatjana C Jakobs, Lei Zhong, Hiroko Wakimoto, Jihad El Andari, Dirk Grimm, Raul Mostoslavsky, Amy J Wagers, Kazuo Tsubota, Stephen J Bonasera, Carlos M Palmeira, Jonathan G Seidman, Christine E Seidman, Norman S Wolf, Jill A Kreiling, John M Sedivy, George F Murphy, Richard E Green, Benjamin A Garcia, Shelley L Berger, Philipp Oberdoerffer, Stuart J Shankland, Vadim N Gladyshev, Bruce R Ksander, Andreas R Pfenning, Luis A Rajman, David A Sinclair","doi":"10.1016/j.cell.2024.01.049","DOIUrl":"https://doi.org/10.1016/j.cell.2024.01.049","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1312-1313"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012239","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.051
{"title":"Five decades of genetics and genomics.","authors":"","doi":"10.1016/j.cell.2024.01.051","DOIUrl":"10.1016/j.cell.2024.01.051","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1017-1018"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012236","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 : 2024-02-29Epub Date: 2024-02-21DOI: 10.1016/j.cell.2024.01.035
Victor Tieu, Elena Sotillo, Jeremy R Bjelajac, Crystal Chen, Meena Malipatlolla, Justin A Guerrero, Peng Xu, Patrick J Quinn, Chris Fisher, Dorota Klysz, Crystal L Mackall, Lei S Qi
{"title":"A versatile CRISPR-Cas13d platform for multiplexed transcriptomic regulation and metabolic engineering in primary human T cells.","authors":"Victor Tieu, Elena Sotillo, Jeremy R Bjelajac, Crystal Chen, Meena Malipatlolla, Justin A Guerrero, Peng Xu, Patrick J Quinn, Chris Fisher, Dorota Klysz, Crystal L Mackall, Lei S Qi","doi":"10.1016/j.cell.2024.01.035","DOIUrl":"10.1016/j.cell.2024.01.035","url":null,"abstract":"<p><p>CRISPR technologies have begun to revolutionize T cell therapies; however, conventional CRISPR-Cas9 genome-editing tools are limited in their safety, efficacy, and scope. To address these challenges, we developed multiplexed effector guide arrays (MEGA), a platform for programmable and scalable regulation of the T cell transcriptome using the RNA-guided, RNA-targeting activity of CRISPR-Cas13d. MEGA enables quantitative, reversible, and massively multiplexed gene knockdown in primary human T cells without targeting or cutting genomic DNA. Applying MEGA to a model of CAR T cell exhaustion, we robustly suppressed inhibitory receptor upregulation and uncovered paired regulators of T cell function through combinatorial CRISPR screening. We additionally implemented druggable regulation of MEGA to control CAR activation in a receptor-independent manner. Lastly, MEGA enabled multiplexed disruption of immunoregulatory metabolic pathways to enhance CAR T cell fitness and anti-tumor activity in vitro and in vivo. MEGA offers a versatile synthetic toolkit for applications in cancer immunotherapy and beyond.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":" ","pages":"1278-1295.e20"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellPub Date : 2024-02-29DOI: 10.1016/j.cell.2024.01.042
Martin Pacesa, Oana Pelea, Martin Jinek
{"title":"Past, present, and future of CRISPR genome editing technologies.","authors":"Martin Pacesa, Oana Pelea, Martin Jinek","doi":"10.1016/j.cell.2024.01.042","DOIUrl":"10.1016/j.cell.2024.01.042","url":null,"abstract":"<p><p>Genome editing has been a transformative force in the life sciences and human medicine, offering unprecedented opportunities to dissect complex biological processes and treat the underlying causes of many genetic diseases. CRISPR-based technologies, with their remarkable efficiency and easy programmability, stand at the forefront of this revolution. In this Review, we discuss the current state of CRISPR gene editing technologies in both research and therapy, highlighting limitations that constrain them and the technological innovations that have been developed in recent years to address them. Additionally, we examine and summarize the current landscape of gene editing applications in the context of human health and therapeutics. Finally, we outline potential future developments that could shape gene editing technologies and their applications in the coming years.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1076-1100"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012240","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.007
Doogab Yi, Janet E Mertz
{"title":"Paul Berg and the origins of recombinant DNA.","authors":"Doogab Yi, Janet E Mertz","doi":"10.1016/j.cell.2024.01.007","DOIUrl":"10.1016/j.cell.2024.01.007","url":null,"abstract":"<p><p>In fall 1972, Paul Berg's laboratory published articles in PNAS describing two methods for constructing recombinant DNAs in vitro. He received half of the 1980 Nobel Prize in Chemistry for this landmark accomplishment. Here, we describe how this discovery came about, revolutionizing both biological research and the pharmaceutical industry.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1019-1023"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012241","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.039
Emily C Fogarty, Matthew S Schechter, Karen Lolans, Madeline L Sheahan, Iva Veseli, Ryan M Moore, Evan Kiefl, Thomas Moody, Phoebe A Rice, Michael K Yu, Mark Mimee, Eugene B Chang, Hans-Joachim Ruscheweyh, Shinichi Sunagawa, Sandra L Mclellan, Amy D Willis, Laurie E Comstock, A Murat Eren
{"title":"A cryptic plasmid is among the most numerous genetic elements in the human gut.","authors":"Emily C Fogarty, Matthew S Schechter, Karen Lolans, Madeline L Sheahan, Iva Veseli, Ryan M Moore, Evan Kiefl, Thomas Moody, Phoebe A Rice, Michael K Yu, Mark Mimee, Eugene B Chang, Hans-Joachim Ruscheweyh, Shinichi Sunagawa, Sandra L Mclellan, Amy D Willis, Laurie E Comstock, A Murat Eren","doi":"10.1016/j.cell.2024.01.039","DOIUrl":"10.1016/j.cell.2024.01.039","url":null,"abstract":"<p><p>Plasmids are extrachromosomal genetic elements that often encode fitness-enhancing features. However, many bacteria carry \"cryptic\" plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes and is 14 times as numerous as crAssphage, currently established as the most abundant extrachromosomal genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from one's mother. pBI143 can transfer between Bacteroidales, and although it does not appear to impact bacterial host fitness in vivo, it can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an alternative approach to track human colonic inflammatory states.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1206-1222.e16"},"PeriodicalIF":45.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellPub Date : 2024-02-29DOI: 10.1016/j.cell.2024.01.034
Yu-Xi Tsai, Ning-En Chang, Klaus Reuter, Hao-Ting Chang, Tzu-Jing Yang, Sören von Bülow, Vidhi Sehrawat, Noémie Zerrouki, Matthieu Tuffery, Michael Gecht, Isabell Louise Grothaus, Lucio Colombi Ciacchi, Yong-Sheng Wang, Min-Feng Hsu, Kay-Hooi Khoo, Gerhard Hummer, Shang-Te Danny Hsu, Cyril Hanus, Mateusz Sikora
{"title":"Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries.","authors":"Yu-Xi Tsai, Ning-En Chang, Klaus Reuter, Hao-Ting Chang, Tzu-Jing Yang, Sören von Bülow, Vidhi Sehrawat, Noémie Zerrouki, Matthieu Tuffery, Michael Gecht, Isabell Louise Grothaus, Lucio Colombi Ciacchi, Yong-Sheng Wang, Min-Feng Hsu, Kay-Hooi Khoo, Gerhard Hummer, Shang-Te Danny Hsu, Cyril Hanus, Mateusz Sikora","doi":"10.1016/j.cell.2024.01.034","DOIUrl":"10.1016/j.cell.2024.01.034","url":null,"abstract":"<p><p>Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1296-1311.e26"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012242","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.043
Ed Hurt, Janet Iwasa, Roland Beckmann
{"title":"SnapShot: Eukaryotic ribosome biogenesis II.","authors":"Ed Hurt, Janet Iwasa, Roland Beckmann","doi":"10.1016/j.cell.2024.01.043","DOIUrl":"10.1016/j.cell.2024.01.043","url":null,"abstract":"<p><p>Ribosome production is essential for cell growth. Approximately 200 assembly factors drive this complicated pathway that starts in the nucleolus and ends in the cytoplasm. A large number of structural snapshots of the pre-60S pathway have revealed the principles behind large subunit synthesis. To view this SnapShot, open or download the PDF.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1314-1314.e1"},"PeriodicalIF":64.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012244","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 : 2024-02-29DOI: 10.1016/j.cell.2024.01.023
Tuuli Lappalainen, Yang I Li, Sohini Ramachandran, Alexander Gusev
{"title":"Genetic and molecular architecture of complex traits.","authors":"Tuuli Lappalainen, Yang I Li, Sohini Ramachandran, Alexander Gusev","doi":"10.1016/j.cell.2024.01.023","DOIUrl":"10.1016/j.cell.2024.01.023","url":null,"abstract":"<p><p>Human genetics has emerged as one of the most dynamic areas of biology, with a broadening societal impact. In this review, we discuss recent achievements, ongoing efforts, and future challenges in the field. Advances in technology, statistical methods, and the growing scale of research efforts have all provided many insights into the processes that have given rise to the current patterns of genetic variation. Vast maps of genetic associations with human traits and diseases have allowed characterization of their genetic architecture. Finally, studies of molecular and cellular effects of genetic variants have provided insights into biological processes underlying disease. Many outstanding questions remain, but the field is well poised for groundbreaking discoveries as it increases the use of genetic data to understand both the history of our species and its applications to improve human health.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"187 5","pages":"1059-1075"},"PeriodicalIF":45.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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