{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:54:34Z","timestamp":1791500074423,"version":"4.3.4"},"posted":{"date-parts":[[2023,4,24]]},"group-title":"Neuroscience","reference-count":93,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,8]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Brain region-specific degeneration and somatic expansions of the mutant Huntingtin (mHTT) CAG tract are key features of Huntington\u2019s disease (HD). However, the relationships between CAG expansions, death of specific cell types, and molecular events associated with these processes are not established. Here we employed fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. CAG expansions arise in striatal medium spiny neurons (MSNs) and cholinergic interneurons, in cerebellar Purkinje neurons, and at\n                  <jats:italic>mATXN3<\/jats:italic>\n                  in MSNs from SCA3 donors. CAG expansions in MSNs are associated with higher levels of MSH2 and MSH3 (forming MutS\u03b2), which can inhibit nucleolytic excision of CAG slip-outs by FAN1 in a concentration-dependent manner. Our data indicate that ongoing CAG expansions are not sufficient for cell death, and identify transcriptional changes associated with somatic CAG expansions and striatal toxicity.\n                <\/jats:p>","DOI":"10.1101\/2023.04.24.538082","type":"posted-content","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T21:15:16Z","timestamp":1682370916000},"source":"Crossref","is-referenced-by-count":15,"title":["Cell Type Specific CAG Repeat Expansions and Toxicity of Mutant Huntingtin in Human Striatum and Cerebellum"],"prefix":"10.64898","author":[{"given":"Kert","family":"M\u00e4tlik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Baffuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit Laxmikant","family":"Deshmukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Masson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Heintz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023061212550963000_2023.04.24.538082v2.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab170"},{"key":"2023061212550963000_2023.04.24.538082v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.12.010"},{"key":"2023061212550963000_2023.04.24.538082v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.003"},{"key":"2023061212550963000_2023.04.24.538082v2.4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00310376"},{"key":"2023061212550963000_2023.04.24.538082v2.5","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198701000-00002"},{"key":"2023061212550963000_2023.04.24.538082v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2008.08.007"},{"key":"2023061212550963000_2023.04.24.538082v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(00)00039-4"},{"key":"2023061212550963000_2023.04.24.538082v2.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"2023061212550963000_2023.04.24.538082v2.9","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370213"},{"key":"2023061212550963000_2023.04.24.538082v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"2023061212550963000_2023.04.24.538082v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/ng0494-409"},{"key":"2023061212550963000_2023.04.24.538082v2.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg352"},{"key":"2023061212550963000_2023.04.24.538082v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.036"},{"key":"2023061212550963000_2023.04.24.538082v2.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003930"},{"key":"2023061212550963000_2023.04.24.538082v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.09.014"},{"key":"2023061212550963000_2023.04.24.538082v2.16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg056"},{"key":"2023061212550963000_2023.04.24.538082v2.17","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200427"},{"key":"2023061212550963000_2023.04.24.538082v2.18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37551"},{"key":"2023061212550963000_2023.04.24.538082v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2781-z"},{"key":"2023061212550963000_2023.04.24.538082v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.029"},{"key":"2023061212550963000_2023.04.24.538082v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.09.010"},{"key":"2023061212550963000_2023.04.24.538082v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2688"},{"key":"2023061212550963000_2023.04.24.538082v2.23","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350116"},{"key":"2023061212550963000_2023.04.24.538082v2.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189990"},{"key":"2023061212550963000_2023.04.24.538082v2.25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa139"},{"key":"2023061212550963000_2023.04.24.538082v2.26","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22177"},{"key":"2023061212550963000_2023.04.24.538082v2.27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm054"},{"key":"2023061212550963000_2023.04.24.538082v2.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.09.020"},{"key":"2023061212550963000_2023.04.24.538082v2.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.15.5733"},{"key":"2023061212550963000_2023.04.24.538082v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63233-3.00009-9"},{"key":"2023061212550963000_2023.04.24.538082v2.31","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.571843"},{"key":"2023061212550963000_2023.04.24.538082v2.32","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25413"},{"key":"2023061212550963000_2023.04.24.538082v2.33","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq501"},{"key":"2023061212550963000_2023.04.24.538082v2.34","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200426"},{"key":"2023061212550963000_2023.04.24.538082v2.35","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz115"},{"key":"2023061212550963000_2023.04.24.538082v2.36","doi-asserted-by":"publisher","DOI":"10.1038\/70598"},{"key":"2023061212550963000_2023.04.24.538082v2.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044273"},{"key":"2023061212550963000_2023.04.24.538082v2.38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003280"},{"key":"2023061212550963000_2023.04.24.538082v2.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.05.012"},{"key":"2023061212550963000_2023.04.24.538082v2.40","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-200448"},{"key":"2023061212550963000_2023.04.24.538082v2.41","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa196"},{"key":"2023061212550963000_2023.04.24.538082v2.42","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy375"},{"key":"2023061212550963000_2023.04.24.538082v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01033-5"},{"key":"2023061212550963000_2023.04.24.538082v2.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110078"},{"key":"2023061212550963000_2023.04.24.538082v2.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.021"},{"key":"2023061212550963000_2023.04.24.538082v2.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174447"},{"key":"2023061212550963000_2023.04.24.538082v2.47","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3101"},{"key":"2023061212550963000_2023.04.24.538082v2.48","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202010179"},{"key":"2023061212550963000_2023.04.24.538082v2.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.03.004"},{"key":"2023061212550963000_2023.04.24.538082v2.50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt635"},{"key":"2023061212550963000_2023.04.24.538082v2.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.01.004"},{"key":"2023061212550963000_2023.04.24.538082v2.52","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.022590"},{"key":"2023061212550963000_2023.04.24.538082v2.53","doi-asserted-by":"publisher","DOI":"10.1086\/512129"},{"key":"2023061212550963000_2023.04.24.538082v2.54","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01349-0"},{"key":"2023061212550963000_2023.04.24.538082v2.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.10.019"},{"key":"2023061212550963000_2023.04.24.538082v2.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.01.006"},{"key":"2023061212550963000_2023.04.24.538082v2.57","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4360"},{"key":"2023061212550963000_2023.04.24.538082v2.58","doi-asserted-by":"publisher","DOI":"10.1002\/syn.1089"},{"key":"2023061212550963000_2023.04.24.538082v2.59","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2012.00629.x"},{"key":"2023061212550963000_2023.04.24.538082v2.60","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(84)90162-6"},{"key":"2023061212550963000_2023.04.24.538082v2.61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900908200"},{"key":"2023061212550963000_2023.04.24.538082v2.62","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10607"},{"key":"2023061212550963000_2023.04.24.538082v2.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102505"},{"key":"2023061212550963000_2023.04.24.538082v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2175"},{"key":"2023061212550963000_2023.04.24.538082v2.65","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb965"},{"key":"2023061212550963000_2023.04.24.538082v2.66","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-71779-1_11"},{"key":"2023061212550963000_2023.04.24.538082v2.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.013"},{"key":"2023061212550963000_2023.04.24.538082v2.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2022.01.005"},{"key":"2023061212550963000_2023.04.24.538082v2.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00641-1"},{"key":"2023061212550963000_2023.04.24.538082v2.70","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0242-x"},{"key":"2023061212550963000_2023.04.24.538082v2.71","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt214"},{"key":"2023061212550963000_2023.04.24.538082v2.72","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"2023061212550963000_2023.04.24.538082v2.73","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.585"},{"key":"2023061212550963000_2023.04.24.538082v2.74","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-019-2879-1"},{"key":"2023061212550963000_2023.04.24.538082v2.75","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3682"},{"key":"2023061212550963000_2023.04.24.538082v2.76","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"2023061212550963000_2023.04.24.538082v2.77","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"2023061212550963000_2023.04.24.538082v2.78","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-210475"},{"key":"2023061212550963000_2023.04.24.538082v2.79","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.101"},{"key":"2023061212550963000_2023.04.24.538082v2.80","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15398.3"},{"key":"2023061212550963000_2023.04.24.538082v2.81","doi-asserted-by":"publisher","DOI":"10.3791\/50320"},{"key":"2023061212550963000_2023.04.24.538082v2.82","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.7.1117"},{"key":"2023061212550963000_2023.04.24.538082v2.83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909087107"},{"key":"2023061212550963000_2023.04.24.538082v2.84","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb959"},{"key":"2023061212550963000_2023.04.24.538082v2.85","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2781-z"},{"key":"2023061212550963000_2023.04.24.538082v2.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110078"},{"key":"2023061212550963000_2023.04.24.538082v2.87","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.028"},{"key":"2023061212550963000_2023.04.24.538082v2.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.01.004"},{"key":"2023061212550963000_2023.04.24.538082v2.89","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.021"},{"key":"2023061212550963000_2023.04.24.538082v2.90","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2022.01.005"},{"key":"2023061212550963000_2023.04.24.538082v2.91","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.029"},{"key":"2023061212550963000_2023.04.24.538082v2.92","doi-asserted-by":"publisher","DOI":"10.1038\/378398a0"},{"key":"2023061212550963000_2023.04.24.538082v2.93","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2002283117"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.04.24.538082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:35:09Z","timestamp":1768451709000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.04.24.538082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,24]]},"references-count":93,"URL":"https:\/\/doi.org\/10.1101\/2023.04.24.538082","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41588-024-01653-6","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,4,24]]},"subtype":"preprint"}}