[{"oa":1,"language":[{"iso":"eng"}],"citation":{"apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"08","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"intvolume":"        20","abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"publication_status":"published","publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"author":[{"orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"last_name":"Miguel Villalba","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","first_name":"Eder","orcid":"0000-0001-5665-0430"},{"last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","last_name":"Watson"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","first_name":"Yoav"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"first_name":"Wiebke","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr"},{"first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"full_name":"Grant, Seth G.N.","last_name":"Grant","first_name":"Seth G.N."},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"last_name":"Bickel","full_name":"Bickel, Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","orcid":"0000-0001-6511-9385"},{"last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G"}],"scopus_import":"1","day":"01","oa_version":"Published Version","title":"Dense 4D nanoscale reconstruction of living brain tissue","volume":20,"article_type":"original","date_created":"2023-07-23T22:01:13Z","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"H2020","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}],"status":"public","publication":"Nature Methods","pmid":1,"ec_funded":1,"date_published":"2023-08-01T00:00:00Z","acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","isi":1,"year":"2023","external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"related_material":{"record":[{"status":"public","relation":"research_data","id":"12817"},{"status":"public","relation":"shorter_version","id":"14770"}],"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}]},"page":"1256-1265","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"quality_controlled":"1","doi":"10.1038/s41592-023-01936-6","article_processing_charge":"Yes","publisher":"Springer Nature","date_updated":"2024-01-10T08:37:48Z","_id":"13267","type":"journal_article"},{"article_type":"original","date_created":"2023-09-03T22:01:15Z","title":"Imaging brain tissue architecture across millimeter to nanometer scales","oa_version":"Published Version","author":[{"orcid":"0000-0003-3862-1235","first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hana","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova"},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"last_name":"Amberg","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"first_name":"Romana","full_name":"Höftberger, Romana","last_name":"Höftberger"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"}],"scopus_import":"1","day":"31","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"publication_status":"epub_ahead","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"month":"08","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>"},"language":[{"iso":"eng"}],"oa":1,"type":"journal_article","date_updated":"2024-02-21T12:18:18Z","_id":"14257","publisher":"Springer Nature","doi":"10.1038/s41587-023-01911-8","article_processing_charge":"Yes (in subscription journal)","quality_controlled":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"external_id":{"isi":["001065254200001"]},"related_material":{"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}],"record":[{"status":"public","relation":"research_data","id":"13126"}]},"year":"2023","isi":1,"date_published":"2023-08-31T00:00:00Z","acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","ec_funded":1,"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"}],"publication":"Nature Biotechnology","status":"public"},{"oa":1,"language":[{"iso":"eng"}],"issue":"1","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","month":"04","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"article_number":"110615","file":[{"success":1,"file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","content_type":"application/pdf","relation":"main_file","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_created":"2022-04-15T09:06:25Z","file_size":"7808644","date_updated":"2022-04-15T09:06:25Z","creator":"dernst","file_id":"11164"}],"has_accepted_license":"1","intvolume":"        39","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publication_status":"published","publication_identifier":{"issn":["2211-1247"]},"file_date_updated":"2022-04-15T09:06:25Z","author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"first_name":"Cristina","last_name":"Cheroni","full_name":"Cheroni, Cristina"},{"orcid":"0000-0002-9033-9096","first_name":"Christoph","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","last_name":"Oliveira"},{"last_name":"Sacco","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","first_name":"Roberto"},{"last_name":"Yahya","full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin"},{"first_name":"Michele","last_name":"Gabriele","full_name":"Gabriele, Michele"},{"orcid":"0000-0002-7667-6854","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"first_name":"Mariano","full_name":"Gabitto, Mariano","last_name":"Gabitto"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"full_name":"Testa, Giuseppe","last_name":"Testa","first_name":"Giuseppe"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178"}],"day":"05","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","oa_version":"Published Version","volume":39,"article_type":"original","date_created":"2022-04-15T09:03:10Z","project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205","call_identifier":"FWF","_id":"2690FEAC-B435-11E9-9278-68D0E5697425"}],"publication":"Cell Reports","status":"public","pmid":1,"ec_funded":1,"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","date_published":"2022-04-05T00:00:00Z","isi":1,"year":"2022","external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12364"}]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"ddc":["570"],"quality_controlled":"1","doi":"10.1016/j.celrep.2022.110615","article_processing_charge":"Yes","publisher":"Elsevier","date_updated":"2024-03-25T23:30:25Z","_id":"11160","type":"journal_article"},{"month":"08","related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"year":"2022","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"language":[{"iso":"eng"}],"status":"public","publication":"bioRxiv","oa":1,"date_published":"2022-08-18T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>."},"publisher":"Cold Spring Harbor Laboratory","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","oa_version":"Preprint","doi":"10.1101/2022.08.17.504272","author":[{"full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G"}],"day":"18","article_processing_charge":"No","type":"preprint","date_created":"2022-08-24T08:24:52Z","date_updated":"2024-03-25T23:30:11Z","_id":"11950","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.","lang":"eng"}],"publication_status":"submitted","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}]}]