[{"article_processing_charge":"No","date_updated":"2026-02-23T10:35:01Z","_id":"21234","issue":"2","has_accepted_license":"1","language":[{"iso":"eng"}],"OA_place":"publisher","OA_type":"hybrid","external_id":{"pmid":["41633365"]},"department":[{"_id":"GradSch"}],"pmid":1,"citation":{"chicago":"Gómez-Pascual, Alicia, Dow M Glikman, Hui Xin Ng, James E. Tomkins, Lu Lu, Ying Xu, David G. Ashbrook, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.cels.2025.101488\">https://doi.org/10.1016/j.cels.2025.101488</a>.","ieee":"A. Gómez-Pascual <i>et al.</i>, “The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus,” <i>Cell Systems</i>, vol. 17, no. 2. Elsevier, 2026.","ama":"Gómez-Pascual A, Glikman DM, Ng HX, et al. The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. <i>Cell Systems</i>. 2026;17(2). doi:<a href=\"https://doi.org/10.1016/j.cels.2025.101488\">10.1016/j.cels.2025.101488</a>","mla":"Gómez-Pascual, Alicia, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>, vol. 17, no. 2, 101488, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.cels.2025.101488\">10.1016/j.cels.2025.101488</a>.","ista":"Gómez-Pascual A, Glikman DM, Ng HX, Tomkins JE, Lu L, Xu Y, Ashbrook DG, Kaczorowski C, Kempermann G, Killmar J, Mozhui K, Ohlenschläger O, Aebersold R, Ingram DK, Williams EG, Jucker M, Overall RW, Williams RW, de Bakker DEM. 2026. The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. Cell Systems. 17(2), 101488.","short":"A. Gómez-Pascual, D.M. Glikman, H.X. Ng, J.E. Tomkins, L. Lu, Y. Xu, D.G. Ashbrook, C. Kaczorowski, G. Kempermann, J. Killmar, K. Mozhui, O. Ohlenschläger, R. Aebersold, D.K. Ingram, E.G. Williams, M. Jucker, R.W. Overall, R.W. Williams, D.E.M. de Bakker, Cell Systems 17 (2026).","apa":"Gómez-Pascual, A., Glikman, D. M., Ng, H. X., Tomkins, J. E., Lu, L., Xu, Y., … de Bakker, D. E. M. (2026). The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2025.101488\">https://doi.org/10.1016/j.cels.2025.101488</a>"},"publication_identifier":{"issn":["2405-4712"]},"oa_version":"Published Version","volume":17,"date_published":"2026-02-18T00:00:00Z","publisher":"Elsevier","publication_status":"published","acknowledgement":"We would like to thank the Summer School Systems Genetics of Neural Ageing for bringing us together and spurring our international collaboration. We would also like to acknowledge the funding for the Summer School 2022 from the e:Med Systems Medicine Program of the BMBF (Bundesministerium für Bildung und Forschung; German Ministry of Education and Research) to R.W.O. In addition, we would like to thank the FLI imaging core facility for their assistance. A.G.-P. is supported by Fundación Séneca, Región de Murcia, Spain (21259/FPI/19). D.E.M.d.B. is financed by a Rubicon scholarship (452021116) from the Dutch Research Council (NWO). This work was also supported by NIH NIA R01AG070913-01 (R.W.W.), R01AG075813-01 (D.G.A.), and R01AG075818 (C.K.). We acknowledge the help of Larry Mobraaten (Jackson Laboratory, Bar Harbor, MN) with the BXD strains and U. Obermüller for the help with the histology. For the purpose of open access, the authors have applied a CC BY public copyright license to all author-accepted manuscripts arising from this submission.","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"license":"https://creativecommons.org/licenses/by/4.0/","publication":"Cell Systems","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2026-02-23T10:32:12Z","intvolume":"        17","month":"02","title":"The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus","PlanS_conform":"1","ddc":["570"],"article_number":"101488","article_type":"original","year":"2026","doi":"10.1016/j.cels.2025.101488","author":[{"last_name":"Gómez-Pascual","first_name":"Alicia","full_name":"Gómez-Pascual, Alicia"},{"last_name":"Glikman","first_name":"Dow M","full_name":"Glikman, Dow M","id":"ab8acda1-91c1-11f0-aad8-f75d3d6424d8"},{"full_name":"Ng, Hui Xin","first_name":"Hui Xin","last_name":"Ng"},{"last_name":"Tomkins","first_name":"James E.","full_name":"Tomkins, James E."},{"full_name":"Lu, Lu","first_name":"Lu","last_name":"Lu"},{"full_name":"Xu, Ying","last_name":"Xu","first_name":"Ying"},{"first_name":"David G.","last_name":"Ashbrook","full_name":"Ashbrook, David G."},{"full_name":"Kaczorowski, Catherine","first_name":"Catherine","last_name":"Kaczorowski"},{"first_name":"Gerd","last_name":"Kempermann","full_name":"Kempermann, Gerd"},{"full_name":"Killmar, John","first_name":"John","last_name":"Killmar"},{"full_name":"Mozhui, Khyobeni","first_name":"Khyobeni","last_name":"Mozhui"},{"full_name":"Ohlenschläger, Oliver","last_name":"Ohlenschläger","first_name":"Oliver"},{"full_name":"Aebersold, Rudolf","first_name":"Rudolf","last_name":"Aebersold"},{"full_name":"Ingram, Donald K.","last_name":"Ingram","first_name":"Donald K."},{"first_name":"Evan G.","last_name":"Williams","full_name":"Williams, Evan G."},{"full_name":"Jucker, Mathias","first_name":"Mathias","last_name":"Jucker"},{"full_name":"Overall, Rupert W.","last_name":"Overall","first_name":"Rupert W."},{"full_name":"Williams, Robert W.","last_name":"Williams","first_name":"Robert W."},{"full_name":"de Bakker, Dennis E.M.","first_name":"Dennis E.M.","last_name":"de Bakker"}],"scopus_import":"1","day":"18","quality_controlled":"1","status":"public","file":[{"file_name":"2026_CellSystems_GomezPascual.pdf","content_type":"application/pdf","date_created":"2026-02-23T10:32:12Z","success":1,"relation":"main_file","creator":"dernst","access_level":"open_access","date_updated":"2026-02-23T10:32:12Z","checksum":"920e8edfd3b8b42f5bb6f86d4c66c54d","file_size":10606778,"file_id":"21349"}],"oa":1,"type":"journal_article","abstract":[{"text":"In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus (Pgb1) that modulates hippocampal PGB burden. Extensive transcriptomic and proteomic datasets were produced for the aged hippocampus of the BXD family to investigate the mechanism by which the Pgb1 locus modulates PGB burden. We identified that Pgb1 contains allelic Smarcal1 and Usp37 variants and influences PGB burden through trans-regulation of mRNA and protein expression levels, including abundance of glycogen-mobilizing factor PYGB. Furthermore, comprehensive phenome-wide association scans, transcriptomic analyses, and direct behavioral testing demonstrated that cognition remains intact despite age-related PGB burden. A record of this paper’s transparent peer review process is included in the supplemental information.","lang":"eng"}],"date_created":"2026-02-16T10:45:10Z"},{"abstract":[{"lang":"eng","text":"Methylation of CG dinucleotides (mCGs), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity is unclear. Whether mCG variation in natural populations is governed by genetic or epigenetic inheritance also remains mysterious. Here, we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z, producing localized mCG patterns. Based on these observations, we develop a stochastic mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing. Our results demonstrate that intragenic mCG establishment, inheritance, and variance constitute a unified epigenetic process, revealing that intragenic mCG undergoes large, millennia-long epigenetic fluctuations and can therefore mediate evolution on this timescale."}],"date_created":"2023-11-19T23:00:54Z","oa":1,"file":[{"file_name":"2023_CellSystems_Briffa.pdf","date_created":"2023-11-20T11:22:52Z","content_type":"application/pdf","success":1,"relation":"main_file","creator":"dernst","access_level":"open_access","date_updated":"2023-11-20T11:22:52Z","checksum":"101fdac59e6f1102d68ef91f2b5bd51a","file_size":5587897,"file_id":"14580"}],"type":"journal_article","corr_author":"1","quality_controlled":"1","status":"public","doi":"10.1016/j.cels.2023.10.007","year":"2023","project":[{"_id":"62935a00-2b32-11ec-9570-eff30fa39068","grant_number":"725746","call_identifier":"H2020","name":"Quantitative analysis of DNA methylation maintenance with chromatin"}],"author":[{"full_name":"Briffa, Amy","first_name":"Amy","last_name":"Briffa"},{"id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd","full_name":"Hollwey, Elizabeth","first_name":"Elizabeth","last_name":"Hollwey"},{"full_name":"Shahzad, Zaigham","last_name":"Shahzad","first_name":"Zaigham"},{"full_name":"Moore, Jonathan D.","last_name":"Moore","first_name":"Jonathan D."},{"first_name":"David B.","last_name":"Lyons","full_name":"Lyons, David B."},{"full_name":"Howard, Martin","last_name":"Howard","first_name":"Martin"},{"id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","full_name":"Zilberman, Daniel","orcid":"0000-0002-0123-8649","last_name":"Zilberman","first_name":"Daniel"}],"scopus_import":"1","page":"953-967","day":"15","article_type":"original","ddc":["570"],"month":"11","title":"Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations","publication":"Cell Systems","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","intvolume":"        14","file_date_updated":"2023-11-20T11:22:52Z","isi":1,"acknowledgement":"We would like to thank Xiaoqi Feng, Ander Movilla Miangolarra, and Suzanne de Bruijn for discussions. This work was supported by BBSRC Institute Strategic Programme GEN (BB/P013511/1) to M.H. and D.Z. and by a European Research Council grant MaintainMeth (725746) to D.Z.","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publisher":"Elsevier","publication_status":"published","oa_version":"Published Version","ec_funded":1,"volume":14,"date_published":"2023-11-15T00:00:00Z","external_id":{"isi":["001113459100001"],"pmid":["37944515"]},"department":[{"_id":"DaZi"}],"pmid":1,"publication_identifier":{"eissn":["2405-4720"],"issn":["2405-4712"]},"citation":{"short":"A. Briffa, E. Hollwey, Z. Shahzad, J.D. Moore, D.B. Lyons, M. Howard, D. Zilberman, Cell Systems 14 (2023) 953–967.","ista":"Briffa A, Hollwey E, Shahzad Z, Moore JD, Lyons DB, Howard M, Zilberman D. 2023. Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. Cell Systems. 14(11), 953–967.","ama":"Briffa A, Hollwey E, Shahzad Z, et al. Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. <i>Cell Systems</i>. 2023;14(11):953-967. doi:<a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">10.1016/j.cels.2023.10.007</a>","mla":"Briffa, Amy, et al. “Millennia-Long Epigenetic Fluctuations Generate Intragenic DNA Methylation Variance in Arabidopsis Populations.” <i>Cell Systems</i>, vol. 14, no. 11, Elsevier, 2023, pp. 953–67, doi:<a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">10.1016/j.cels.2023.10.007</a>.","apa":"Briffa, A., Hollwey, E., Shahzad, Z., Moore, J. D., Lyons, D. B., Howard, M., &#38; Zilberman, D. (2023). Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">https://doi.org/10.1016/j.cels.2023.10.007</a>","ieee":"A. Briffa <i>et al.</i>, “Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations,” <i>Cell Systems</i>, vol. 14, no. 11. Elsevier, pp. 953–967, 2023.","chicago":"Briffa, Amy, Elizabeth Hollwey, Zaigham Shahzad, Jonathan D. Moore, David B. Lyons, Martin Howard, and Daniel Zilberman. “Millennia-Long Epigenetic Fluctuations Generate Intragenic DNA Methylation Variance in Arabidopsis Populations.” <i>Cell Systems</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">https://doi.org/10.1016/j.cels.2023.10.007</a>."},"has_accepted_license":"1","language":[{"iso":"eng"}],"issue":"11","article_processing_charge":"Yes (via OA deal)","date_updated":"2025-09-09T13:28:50Z","_id":"14551"},{"external_id":{"pmid":["35452605"],"isi":["000814124400002"]},"publication_identifier":{"issn":["2405-4712"],"eissn":["2405-4720"]},"citation":{"apa":"Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., &#38; Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">https://doi.org/10.1016/j.cels.2022.03.006</a>","short":"D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, Cell Systems 13 (2022) 438–453.e5.","ista":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 13(6), 438–453.e5.","ama":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. <i>Cell Systems</i>. 2022;13(6):438-453.e5. doi:<a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">10.1016/j.cels.2022.03.006</a>","mla":"Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” <i>Cell Systems</i>, vol. 13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:<a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">10.1016/j.cels.2022.03.006</a>.","ieee":"D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development,” <i>Cell Systems</i>, vol. 13, no. 6. Elsevier, p. 438–453.e5, 2022.","chicago":"Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” <i>Cell Systems</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.cels.2022.03.006\">https://doi.org/10.1016/j.cels.2022.03.006</a>."},"department":[{"_id":"SiHi"}],"pmid":1,"language":[{"iso":"eng"}],"issue":"6","date_updated":"2025-04-14T07:43:05Z","article_processing_charge":"No","_id":"11449","publication":"Cell Systems","intvolume":"        13","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program 725780 LinPro to S.H.","isi":1,"publication_status":"published","publisher":"Elsevier","ec_funded":1,"oa_version":"Published Version","volume":13,"date_published":"2022-06-15T00:00:00Z","project":[{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"author":[{"full_name":"Anderson, Donovan J.","last_name":"Anderson","first_name":"Donovan J."},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048"},{"full_name":"Mckenna, Aaron","last_name":"Mckenna","first_name":"Aaron"},{"first_name":"Jay","last_name":"Shendure","full_name":"Shendure, Jay"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"},{"first_name":"Marshall S.","last_name":"Horwitz","full_name":"Horwitz, Marshall S."}],"doi":"10.1016/j.cels.2022.03.006","year":"2022","day":"15","scopus_import":"1","page":"438-453.e5","article_type":"original","month":"06","title":"Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development","abstract":[{"lang":"eng","text":"Mutations are acquired frequently, such that each cell's genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide variants (SNVs). We simultaneously inferred cell lineage and marked developmental time points based on X chromosome inactivation and the total number of LOH events while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared with experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans."}],"main_file_link":[{"url":"https://doi.org/10.1016/j.cels.2022.03.006","open_access":"1"}],"date_created":"2022-06-19T22:01:57Z","oa":1,"type":"journal_article","quality_controlled":"1","status":"public"},{"article_type":"original","day":"27","page":"423-433.e1-e3","scopus_import":"1","author":[{"full_name":"Lukacisin, Martin","id":"298FFE8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6549-4177","last_name":"Lukacisin","first_name":"Martin"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","first_name":"Tobias"}],"project":[{"_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions"},{"name":"Revealing the fundamental limits of cell growth","grant_number":"RGP0042/2013","_id":"25EB3A80-B435-11E9-9278-68D0E5697425"}],"year":"2019","doi":"10.1016/j.cels.2019.10.004","title":"Emergent gene expression responses to drug combinations predict higher-order drug interactions","month":"11","ddc":["570"],"type":"journal_article","acknowledged_ssus":[{"_id":"LifeSc"}],"oa":1,"file":[{"date_created":"2019-11-15T10:57:42Z","content_type":"application/pdf","file_name":"2019_CellSystems_Lukacisin.pdf","date_updated":"2020-07-14T12:47:48Z","access_level":"open_access","creator":"dernst","relation":"main_file","file_id":"7027","file_size":4238460,"checksum":"7a11d6c2f9523d65b049512d61733178"}],"date_created":"2019-11-15T10:51:42Z","abstract":[{"text":"Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information.","lang":"eng"}],"status":"public","quality_controlled":"1","language":[{"iso":"eng"}],"has_accepted_license":"1","citation":{"chicago":"Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression Responses to Drug Combinations Predict Higher-Order Drug Interactions.” <i>Cell Systems</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">https://doi.org/10.1016/j.cels.2019.10.004</a>.","ieee":"M. Lukacisin and M. T. Bollenbach, “Emergent gene expression responses to drug combinations predict higher-order drug interactions,” <i>Cell Systems</i>, vol. 9, no. 5. Cell Press, pp. 423-433.e1-e3, 2019.","apa":"Lukacisin, M., &#38; Bollenbach, M. T. (2019). Emergent gene expression responses to drug combinations predict higher-order drug interactions. <i>Cell Systems</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">https://doi.org/10.1016/j.cels.2019.10.004</a>","mla":"Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression Responses to Drug Combinations Predict Higher-Order Drug Interactions.” <i>Cell Systems</i>, vol. 9, no. 5, Cell Press, 2019, pp. 423-433.e1-e3, doi:<a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">10.1016/j.cels.2019.10.004</a>.","ama":"Lukacisin M, Bollenbach MT. Emergent gene expression responses to drug combinations predict higher-order drug interactions. <i>Cell Systems</i>. 2019;9(5):423-433.e1-e3. doi:<a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">10.1016/j.cels.2019.10.004</a>","ista":"Lukacisin M, Bollenbach MT. 2019. Emergent gene expression responses to drug combinations predict higher-order drug interactions. Cell Systems. 9(5), 423-433.e1-e3.","short":"M. Lukacisin, M.T. Bollenbach, Cell Systems 9 (2019) 423-433.e1-e3."},"publication_identifier":{"issn":["2405-4712"]},"department":[{"_id":"ToBo"}],"external_id":{"isi":["000499495400003"]},"_id":"7026","date_updated":"2025-04-15T08:09:37Z","article_processing_charge":"No","issue":"5","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"intvolume":"         9","file_date_updated":"2020-07-14T12:47:48Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"Cell Systems","date_published":"2019-11-27T00:00:00Z","volume":9,"oa_version":"Published Version","publication_status":"published","publisher":"Cell Press"},{"corr_author":"1","status":"public","quality_controlled":"1","date_created":"2018-12-11T11:47:48Z","abstract":[{"text":"Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to “cross-protect” bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors.","lang":"eng"}],"type":"journal_article","oa":1,"file":[{"content_type":"application/pdf","date_created":"2018-12-12T10:13:54Z","file_name":"IST-2017-901-v1+1_1-s2.0-S2405471217300868-main.pdf","date_updated":"2020-07-14T12:47:35Z","access_level":"open_access","creator":"system","relation":"main_file","file_id":"5041","file_size":2438660,"checksum":"04ff20011c3d9a601c514aa999a5fe1a"}],"pubrep_id":"901","related_material":{"record":[{"id":"818","status":"public","relation":"dissertation_contains"}]},"ddc":["576","610"],"title":"Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment","month":"04","scopus_import":"1","page":"393 - 403","day":"26","year":"2017","doi":"10.1016/j.cels.2017.03.001","project":[{"_id":"25E83C2C-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"303507","name":"Optimality principles in responses to antibiotics"},{"_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22","call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions"},{"name":"Revealing the fundamental limits of cell growth","_id":"25EB3A80-B435-11E9-9278-68D0E5697425","grant_number":"RGP0042/2013"}],"author":[{"id":"39B66846-F248-11E8-B48F-1D18A9856A87","full_name":"Mitosch, Karin","first_name":"Karin","last_name":"Mitosch"},{"id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87","full_name":"Rieckh, Georg","last_name":"Rieckh","first_name":"Georg"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","first_name":"Tobias","last_name":"Bollenbach"}],"publisher":"Cell Press","publication_status":"published","date_published":"2017-04-26T00:00:00Z","volume":4,"oa_version":"Published Version","ec_funded":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file_date_updated":"2020-07-14T12:47:35Z","intvolume":"         4","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publication":"Cell Systems","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"isi":1,"issue":"4","_id":"666","article_processing_charge":"Yes (in subscription journal)","date_updated":"2026-04-08T14:21:56Z","department":[{"_id":"ToBo"},{"_id":"GaTk"}],"citation":{"chicago":"Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Noisy Response to Antibiotic Stress Predicts Subsequent Single Cell Survival in an Acidic Environment.” <i>Cell Systems</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cels.2017.03.001\">https://doi.org/10.1016/j.cels.2017.03.001</a>.","ieee":"K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment,” <i>Cell Systems</i>, vol. 4, no. 4. Cell Press, pp. 393–403, 2017.","mla":"Mitosch, Karin, et al. “Noisy Response to Antibiotic Stress Predicts Subsequent Single Cell Survival in an Acidic Environment.” <i>Cell Systems</i>, vol. 4, no. 4, Cell Press, 2017, pp. 393–403, doi:<a href=\"https://doi.org/10.1016/j.cels.2017.03.001\">10.1016/j.cels.2017.03.001</a>.","ama":"Mitosch K, Rieckh G, Bollenbach MT. Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment. <i>Cell Systems</i>. 2017;4(4):393-403. doi:<a href=\"https://doi.org/10.1016/j.cels.2017.03.001\">10.1016/j.cels.2017.03.001</a>","short":"K. Mitosch, G. Rieckh, M.T. Bollenbach, Cell Systems 4 (2017) 393–403.","ista":"Mitosch K, Rieckh G, Bollenbach MT. 2017. Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment. Cell Systems. 4(4), 393–403.","apa":"Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2017). Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment. <i>Cell Systems</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cels.2017.03.001\">https://doi.org/10.1016/j.cels.2017.03.001</a>"},"publication_identifier":{"issn":["2405-4712"]},"external_id":{"isi":["000402747300005"]},"publist_id":"7061","has_accepted_license":"1","language":[{"iso":"eng"}]},{"title":"Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats","month":"09","article_type":"original","scopus_import":"1","page":"P224-237","day":"23","doi":"10.1016/j.cels.2015.08.012","year":"2015","author":[{"full_name":"Ori, Alessandro","first_name":"Alessandro","last_name":"Ori"},{"last_name":"Toyama","first_name":"Brandon H.","full_name":"Toyama, Brandon H."},{"full_name":"Harris, Michael S.","last_name":"Harris","first_name":"Michael S."},{"first_name":"Thomas","last_name":"Bock","full_name":"Bock, Thomas"},{"first_name":"Murat","last_name":"Iskar","full_name":"Iskar, Murat"},{"full_name":"Bork, Peer","first_name":"Peer","last_name":"Bork"},{"full_name":"Ingolia, Nicholas T.","first_name":"Nicholas T.","last_name":"Ingolia"},{"id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"HETZER, Martin W","first_name":"Martin W","last_name":"HETZER","orcid":"0000-0002-2111-992X"},{"full_name":"Beck, Martin","last_name":"Beck","first_name":"Martin"}],"status":"public","quality_controlled":"1","type":"journal_article","oa":1,"keyword":["Cell Biology","Histology","Pathology and Forensic Medicine"],"date_created":"2022-04-07T07:49:39Z","main_file_link":[{"url":"https://doi.org/10.1016/j.cels.2015.08.012","open_access":"1"}],"abstract":[{"lang":"eng","text":"Aging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats’ chronological age, the majority are specific to one organ. These may be a consequence of the organ’s physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats."}],"_id":"11078","article_processing_charge":"No","date_updated":"2024-10-14T11:23:01Z","issue":"3","extern":"1","language":[{"iso":"eng"}],"pmid":1,"citation":{"ieee":"A. Ori <i>et al.</i>, “Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats,” <i>Cell Systems</i>, vol. 1, no. 3. Elsevier, pp. P224-237, 2015.","chicago":"Ori, Alessandro, Brandon H. Toyama, Michael S. Harris, Thomas Bock, Murat Iskar, Peer Bork, Nicholas T. Ingolia, Martin Hetzer, and Martin Beck. “Integrated Transcriptome and Proteome Analyses Reveal Organ-Specific Proteome Deterioration in Old Rats.” <i>Cell Systems</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.cels.2015.08.012\">https://doi.org/10.1016/j.cels.2015.08.012</a>.","apa":"Ori, A., Toyama, B. H., Harris, M. S., Bock, T., Iskar, M., Bork, P., … Beck, M. (2015). Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2015.08.012\">https://doi.org/10.1016/j.cels.2015.08.012</a>","short":"A. Ori, B.H. Toyama, M.S. Harris, T. Bock, M. Iskar, P. Bork, N.T. Ingolia, M. Hetzer, M. Beck, Cell Systems 1 (2015) P224-237.","ista":"Ori A, Toyama BH, Harris MS, Bock T, Iskar M, Bork P, Ingolia NT, Hetzer M, Beck M. 2015. Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats. Cell Systems. 1(3), P224-237.","ama":"Ori A, Toyama BH, Harris MS, et al. Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats. <i>Cell Systems</i>. 2015;1(3):P224-237. doi:<a href=\"https://doi.org/10.1016/j.cels.2015.08.012\">10.1016/j.cels.2015.08.012</a>","mla":"Ori, Alessandro, et al. “Integrated Transcriptome and Proteome Analyses Reveal Organ-Specific Proteome Deterioration in Old Rats.” <i>Cell Systems</i>, vol. 1, no. 3, Elsevier, 2015, pp. P224-237, doi:<a href=\"https://doi.org/10.1016/j.cels.2015.08.012\">10.1016/j.cels.2015.08.012</a>."},"publication_identifier":{"issn":["2405-4712"]},"external_id":{"pmid":["27135913"]},"volume":1,"date_published":"2015-09-23T00:00:00Z","oa_version":"Published Version","publisher":"Elsevier","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"         1","publication":"Cell Systems"}]