{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:58:57Z","timestamp":1790164737726,"version":"4.1.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,5,11]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Although the genetic basis of HD is known, the molecular mechanisms underlying neuronal dysfunction remain unclear. Combining electrophysiological and transcriptional analyses of single neurons (Patch-sequencing [Patch-seq]), this study connects transcriptional dysregulation and synaptic transmission deficits, two key disease features, in HD. We identify a number of genes whose expression changes are correlated with physiological deficiencies in mutant Htt neurons. We validate the use of the Patch-seq system for screening and identifying potential therapeutic interventions. We show that pharmacological inhibition of an epigenetic regulator rectifies several functional, morphological, and transcriptional deficits in mutant neurons. This work suggests previously unknown gene\u2013neuronal function relationships as potential targets in HD and also highlights advances in single-cell transcriptomics and their use in understanding human disease.<\/jats:p>","DOI":"10.1073\/pnas.2020293118","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T15:57:15Z","timestamp":1620230235000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington\u2019s disease"],"prefix":"10.1073","volume":"118","author":[{"given":"Foteini","family":"Paraskevopoulou","sequence":"first","affiliation":[{"name":"Department of Neurophysiology, Charite\u0301\u2013Universita\u0308tsmedizin Berlin, 10117 Berlin, Germany;"},{"name":"NeuroCure Cluster of Excellence, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-765X","authenticated-orcid":false,"given":"Poorya","family":"Parvizi","sequence":"additional","affiliation":[{"name":"Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, 06500 Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-8206","authenticated-orcid":false,"given":"G\u00f6k\u00e7e","family":"Senger","sequence":"additional","affiliation":[{"name":"Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, 06500 Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurcan","family":"Tuncbag","sequence":"additional","affiliation":[{"name":"Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, 06500 Ankara, Turkey;"},{"name":"Department of Chemical and Biological Engineering, College of Engineering, Koc University, 34450 Istanbul, Turkey;"},{"name":"School of Medicine, Koc University, 34450 Istanbul, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3905-2444","authenticated-orcid":false,"given":"Christian","family":"Rosenmund","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Charite\u0301\u2013Universita\u0308tsmedizin Berlin, 10117 Berlin, Germany;"},{"name":"NeuroCure Cluster of Excellence, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferah","family":"Yildirim","sequence":"additional","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany;"},{"name":"Department of Neuropsychiatry, Department of Psychiatry and Psychotherapy, Charite\u0301\u2013Universita\u0308tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91524-0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1971.0102"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn025"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.08.052"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.02.017"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.08.006"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7626"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90346-1"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00611-6"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2004.01.008"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6480"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1259"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-2772(03)00059-8"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4256"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311323110"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908113116"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl013"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7834"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3445"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201540945"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1954.sp005129"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00643-3"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80146-4"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.158"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.07.001"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.021"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz401"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-57369-0"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw036"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz174"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.08.035"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15592"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm133"},{"key":"e_1_3_4_38_2","unstructured":"L. Francelle \u201cA study of striatal markers as disease modifiers in Huntington\u2019s disease \u201d Doctroral thesis Universit\u00e9 Paris Sud - Paris XI Orsay France (2014)."},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24320"},{"key":"e_1_3_4_40_2","first-page":"4317","article-title":"Identification of differentially expressed genes and regulatory relationships in Huntington\u2019s disease by bioinformatics analysis","volume":"17","author":"Dong X.","year":"2018","unstructured":"X. Dong, S. Cong, Identification of differentially expressed genes and regulatory relationships in Huntington\u2019s disease by bioinformatics analysis. Mol. Med. Rep. 17, 4317\u20134326 (2018).","journal-title":"Mol. Med. Rep."},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1134\/S002689331704015X"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2137-12.2013"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1244"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991115)58:4<515::AID-JNR5>3.0.CO;2-F"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00791.2004"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056784"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.06.029"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0229-17.2018"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.01.003"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2630-18.2019"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaf6670"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.351"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.6358.1"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4532"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.01.016"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415195112"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01358-7"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4992-08.2010"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0187-13.2013"},{"key":"e_1_3_4_61_2","doi-asserted-by":"crossref","unstructured":"F. Paraskevopoulou Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington\u2019s disease. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE171099. Deposited 29 March 2021.","DOI":"10.1073\/pnas.2020293118"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.059"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2020293118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:05:03Z","timestamp":1649829903000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2020293118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":62,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2021,5,11]]}},"alternative-id":["10.1073\/pnas.2020293118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2020293118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2020293118"}}