CellPub Date : 2023-09-14Epub Date: 2023-08-08DOI: 10.1016/j.cell.2023.07.010
Shukun Wang, Clinton Gabel, Romana Siddique, Thomas Klose, Leifu Chang
{"title":"Molecular mechanism for Tn7-like transposon recruitment by a type I-B CRISPR effector.","authors":"Shukun Wang, Clinton Gabel, Romana Siddique, Thomas Klose, Leifu Chang","doi":"10.1016/j.cell.2023.07.010","DOIUrl":"10.1016/j.cell.2023.07.010","url":null,"abstract":"<p><p>Tn7-like transposons have co-opted CRISPR-Cas systems to facilitate the movement of their own DNA. These CRISPR-associated transposons (CASTs) are promising tools for programmable gene knockin. A key feature of CASTs is their ability to recruit Tn7-like transposons to nuclease-deficient CRISPR effectors. However, how Tn7-like transposons are recruited by diverse CRISPR effectors remains poorly understood. Here, we present the cryo-EM structure of a recruitment complex comprising the Cascade complex, TniQ, TnsC, and the target DNA in the type I-B CAST from Peltigera membranacea cyanobiont 210A. Target DNA recognition by Cascade induces conformational changes in Cas6 and primes TniQ recruitment through its C-terminal domain. The N-terminal domain of TniQ is bound to the seam region of the TnsC spiral heptamer. Our findings provide insights into the diverse mechanisms for the recruitment of Tn7-like transposons to CRISPR effectors and will aid in the development of CASTs as gene knockin tools.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 19","pages":"4204-4215.e19"},"PeriodicalIF":45.5,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274333","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 : 2023-09-14Epub Date: 2023-09-06DOI: 10.1016/j.cell.2023.08.016
Susan R Davis, JoAnn Pinkerton, Nanette Santoro, Tommaso Simoncini
{"title":"Menopause-Biology, consequences, supportive care, and therapeutic options.","authors":"Susan R Davis, JoAnn Pinkerton, Nanette Santoro, Tommaso Simoncini","doi":"10.1016/j.cell.2023.08.016","DOIUrl":"10.1016/j.cell.2023.08.016","url":null,"abstract":"<p><p>Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 19","pages":"4038-4058"},"PeriodicalIF":64.5,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276320","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 : 2023-09-14DOI: 10.1016/j.cell.2023.08.006
Kevin G Mark, SriDurgaDevi Kolla, Jacob D Aguirre, Danielle M Garshott, Stefan Schmitt, Diane L Haakonsen, Christina Xu, Lukas Kater, Georg Kempf, Brenda Martínez-González, David Akopian, Stephanie K See, Nicolas H Thomä, Michael Rapé
{"title":"Orphan quality control shapes network dynamics and gene expression.","authors":"Kevin G Mark, SriDurgaDevi Kolla, Jacob D Aguirre, Danielle M Garshott, Stefan Schmitt, Diane L Haakonsen, Christina Xu, Lukas Kater, Georg Kempf, Brenda Martínez-González, David Akopian, Stephanie K See, Nicolas H Thomä, Michael Rapé","doi":"10.1016/j.cell.2023.08.006","DOIUrl":"https://doi.org/10.1016/j.cell.2023.08.006","url":null,"abstract":"","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 19","pages":"4252-4253"},"PeriodicalIF":64.5,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10265568","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 : 2023-09-14Epub Date: 2023-08-28DOI: 10.1016/j.cell.2023.08.001
Seung Cho Lee, Dexter W Adams, Jonathan J Ipsaro, Jonathan Cahn, Jason Lynn, Hyun-Soo Kim, Benjamin Berube, Viktoria Major, Joseph P Calarco, Chantal LeBlanc, Sonali Bhattacharjee, Umamaheswari Ramu, Daniel Grimanelli, Yannick Jacob, Philipp Voigt, Leemor Joshua-Tor, Robert A Martienssen
{"title":"Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.","authors":"Seung Cho Lee, Dexter W Adams, Jonathan J Ipsaro, Jonathan Cahn, Jason Lynn, Hyun-Soo Kim, Benjamin Berube, Viktoria Major, Joseph P Calarco, Chantal LeBlanc, Sonali Bhattacharjee, Umamaheswari Ramu, Daniel Grimanelli, Yannick Jacob, Philipp Voigt, Leemor Joshua-Tor, Robert A Martienssen","doi":"10.1016/j.cell.2023.08.001","DOIUrl":"10.1016/j.cell.2023.08.001","url":null,"abstract":"<p><p>Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1<sup>LSH</sup><sup><sup>/</sup>HELLS</sup>), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.1. In ddm1 mutants, DNA methylation is partly restored by loss of the H3.3 chaperone HIRA, while the H3.1 chaperone CAF-1 becomes essential. The single-particle cryo-EM structure at 3.2 Å of DDM1 with a variant nucleosome reveals engagement with histone H3.3 near residues required for assembly and with the unmodified H4 tail. An N-terminal autoinhibitory domain inhibits activity, while a disulfide bond in the helicase domain supports activity. DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1<sup>Dnmt1</sup>, but is blocked by H4K16 acetylation. The male germline H3.3 variant MGH3/HTR10 is resistant to remodeling by DDM1 and acts as a placeholder nucleosome in sperm cells for epigenetic inheritance.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 19","pages":"4100-4116.e15"},"PeriodicalIF":64.5,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283314","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 : 2023-08-31DOI: 10.1016/j.cell.2023.08.003
Mahdi Moqri, Chiara Herzog, Jesse R Poganik, Jamie Justice, Daniel W Belsky, Albert Higgins-Chen, Alexey Moskalev, Georg Fuellen, Alan A Cohen, Ivan Bautmans, Martin Widschwendter, Jingzhong Ding, Alexander Fleming, Joan Mannick, Jing-Dong Jackie Han, Alex Zhavoronkov, Nir Barzilai, Matt Kaeberlein, Steven Cummings, Brian K Kennedy, Luigi Ferrucci, Steve Horvath, Eric Verdin, Andrea B Maier, Michael P Snyder, Vittorio Sebastiano, Vadim N Gladyshev
{"title":"Biomarkers of aging for the identification and evaluation of longevity interventions.","authors":"Mahdi Moqri, Chiara Herzog, Jesse R Poganik, Jamie Justice, Daniel W Belsky, Albert Higgins-Chen, Alexey Moskalev, Georg Fuellen, Alan A Cohen, Ivan Bautmans, Martin Widschwendter, Jingzhong Ding, Alexander Fleming, Joan Mannick, Jing-Dong Jackie Han, Alex Zhavoronkov, Nir Barzilai, Matt Kaeberlein, Steven Cummings, Brian K Kennedy, Luigi Ferrucci, Steve Horvath, Eric Verdin, Andrea B Maier, Michael P Snyder, Vittorio Sebastiano, Vadim N Gladyshev","doi":"10.1016/j.cell.2023.08.003","DOIUrl":"10.1016/j.cell.2023.08.003","url":null,"abstract":"<p><p>With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 18","pages":"3758-3775"},"PeriodicalIF":64.5,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10504972","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 : 2023-08-31Epub Date: 2023-08-18DOI: 10.1016/j.cell.2023.07.019
Jin-Gyu Cheong, Arjun Ravishankar, Siddhartha Sharma, Christopher N Parkhurst, Simon A Grassmann, Claire K Wingert, Paoline Laurent, Sai Ma, Lucinda Paddock, Isabella C Miranda, Emin Onur Karakaslar, Djamel Nehar-Belaid, Asa Thibodeau, Michael J Bale, Vinay K Kartha, Jim K Yee, Minh Y Mays, Chenyang Jiang, Andrew W Daman, Alexia Martinez de Paz, Dughan Ahimovic, Victor Ramos, Alexander Lercher, Erik Nielsen, Sergio Alvarez-Mulett, Ling Zheng, Andrew Earl, Alisha Yallowitz, Lexi Robbins, Elyse LaFond, Karissa L Weidman, Sabrina Racine-Brzostek, He S Yang, David R Price, Louise Leyre, André F Rendeiro, Hiranmayi Ravichandran, Junbum Kim, Alain C Borczuk, Charles M Rice, R Brad Jones, Edward J Schenck, Robert J Kaner, Amy Chadburn, Zhen Zhao, Virginia Pascual, Olivier Elemento, Robert E Schwartz, Jason D Buenrostro, Rachel E Niec, Franck J Barrat, Lindsay Lief, Joseph C Sun, Duygu Ucar, Steven Z Josefowicz
{"title":"Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.","authors":"Jin-Gyu Cheong, Arjun Ravishankar, Siddhartha Sharma, Christopher N Parkhurst, Simon A Grassmann, Claire K Wingert, Paoline Laurent, Sai Ma, Lucinda Paddock, Isabella C Miranda, Emin Onur Karakaslar, Djamel Nehar-Belaid, Asa Thibodeau, Michael J Bale, Vinay K Kartha, Jim K Yee, Minh Y Mays, Chenyang Jiang, Andrew W Daman, Alexia Martinez de Paz, Dughan Ahimovic, Victor Ramos, Alexander Lercher, Erik Nielsen, Sergio Alvarez-Mulett, Ling Zheng, Andrew Earl, Alisha Yallowitz, Lexi Robbins, Elyse LaFond, Karissa L Weidman, Sabrina Racine-Brzostek, He S Yang, David R Price, Louise Leyre, André F Rendeiro, Hiranmayi Ravichandran, Junbum Kim, Alain C Borczuk, Charles M Rice, R Brad Jones, Edward J Schenck, Robert J Kaner, Amy Chadburn, Zhen Zhao, Virginia Pascual, Olivier Elemento, Robert E Schwartz, Jason D Buenrostro, Rachel E Niec, Franck J Barrat, Lindsay Lief, Joseph C Sun, Duygu Ucar, Steven Z Josefowicz","doi":"10.1016/j.cell.2023.07.019","DOIUrl":"10.1016/j.cell.2023.07.019","url":null,"abstract":"<p><p>Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 18","pages":"3882-3902.e24"},"PeriodicalIF":45.5,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531722","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 : 2023-08-31DOI: 10.1016/j.cell.2023.07.039
Jordan L Doman, Smriti Pandey, Monica E Neugebauer, Meirui An, Jessie R Davis, Peyton B Randolph, Amber McElroy, Xin D Gao, Aditya Raguram, Michelle F Richter, Kelcee A Everette, Samagya Banskota, Kathryn Tian, Y Allen Tao, Jakub Tolar, Mark J Osborn, David R Liu
{"title":"Phage-assisted evolution and protein engineering yield compact, efficient prime editors.","authors":"Jordan L Doman, Smriti Pandey, Monica E Neugebauer, Meirui An, Jessie R Davis, Peyton B Randolph, Amber McElroy, Xin D Gao, Aditya Raguram, Michelle F Richter, Kelcee A Everette, Samagya Banskota, Kathryn Tian, Y Allen Tao, Jakub Tolar, Mark J Osborn, David R Liu","doi":"10.1016/j.cell.2023.07.039","DOIUrl":"10.1016/j.cell.2023.07.039","url":null,"abstract":"<p><p>Prime editing enables a wide variety of precise genome edits in living cells. Here we use protein evolution and engineering to generate prime editors with reduced size and improved efficiency. Using phage-assisted evolution, we improved editing efficiencies of compact reverse transcriptases by up to 22-fold and generated prime editors that are 516-810 base pairs smaller than the current-generation editor PEmax. We discovered that different reverse transcriptases specialize in different types of edits and used this insight to generate reverse transcriptases that outperform PEmax and PEmaxΔRNaseH, the truncated editor used in dual-AAV delivery systems. Finally, we generated Cas9 domains that improve prime editing. These resulting editors (PE6a-g) enhance therapeutically relevant editing in patient-derived fibroblasts and primary human T-cells. PE6 variants also enable longer insertions to be installed in vivo following dual-AAV delivery, achieving 40% loxP insertion in the cortex of the murine brain, a 24-fold improvement compared to previous state-of-the-art prime editors.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 18","pages":"3983-4002.e26"},"PeriodicalIF":64.5,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10559332","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 : 2023-08-31Epub Date: 2023-08-08DOI: 10.1016/j.cell.2023.07.016
Xufeng Chen, Qiao Lu, Hua Zhou, Jia Liu, Bettina Nadorp, Audrey Lasry, Zhengxi Sun, Baoling Lai, Gergely Rona, Jiangyan Zhang, Michael Cammer, Kun Wang, Wafa Al-Santli, Zoe Ciantra, Qianjin Guo, Jia You, Debrup Sengupta, Ahmad Boukhris, Hongbing Zhang, Cheng Liu, Peter Cresswell, Patricia L M Dahia, Michele Pagano, Iannis Aifantis, Jun Wang
{"title":"A membrane-associated MHC-I inhibitory axis for cancer immune evasion.","authors":"Xufeng Chen, Qiao Lu, Hua Zhou, Jia Liu, Bettina Nadorp, Audrey Lasry, Zhengxi Sun, Baoling Lai, Gergely Rona, Jiangyan Zhang, Michael Cammer, Kun Wang, Wafa Al-Santli, Zoe Ciantra, Qianjin Guo, Jia You, Debrup Sengupta, Ahmad Boukhris, Hongbing Zhang, Cheng Liu, Peter Cresswell, Patricia L M Dahia, Michele Pagano, Iannis Aifantis, Jun Wang","doi":"10.1016/j.cell.2023.07.016","DOIUrl":"10.1016/j.cell.2023.07.016","url":null,"abstract":"<p><p>Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, we identified key MHC-I regulators using specific peptide-MHC-I-guided CRISPR-Cas9 screens in AML. The top-ranked negative regulators were surface protein sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. SUSD6 is abundantly expressed in AML and multiple solid cancers, and its ablation enhanced MHC-I AP and reduced tumor growth in a CD8<sup>+</sup> T cell-dependent manner. Mechanistically, SUSD6 forms a trimolecular complex with TMEM127 and MHC-I, which recruits WWP2 for MHC-I ubiquitination and lysosomal degradation. Together with the SUSD6/TMEM127/WWP2 gene signature, which negatively correlates with cancer survival, our findings define a membrane-associated MHC-I inhibitory axis as a potential therapeutic target for both leukemia and solid cancers.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 18","pages":"3903-3920.e21"},"PeriodicalIF":45.5,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489909","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 : 2023-08-31Epub Date: 2023-08-15DOI: 10.1016/j.cell.2023.07.024
Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L van der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin
{"title":"Archival single-cell genomics reveals persistent subclones during DCIS progression.","authors":"Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L van der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin","doi":"10.1016/j.cell.2023.07.024","DOIUrl":"10.1016/j.cell.2023.07.024","url":null,"abstract":"<p><p>Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"186 18","pages":"3968-3982.e15"},"PeriodicalIF":64.5,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168955","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
