[{"article_processing_charge":"Yes","volume":24,"external_id":{"pmid":["34426698 "],"isi":["000687516300001"]},"date_created":"2019-11-10T11:23:58Z","page":"32","type":"technical_report","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"language":[{"iso":"eng"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","title":"Identification of neural oscillations and epileptiform changes in human brain organoids","alternative_title":["Nature Neuroscience"],"pmid":1,"acknowledgement":"We thank S. Butler, T. Carmichael and members of the laboratory of B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities Research Center microscopy cores for access to imaging facilities. This work was supported by grants from the California Institute for Regenerative Medicine (CIRM) (DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897 and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922, R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.; R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program (to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S. and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience Training Grant (R25NS065723), a Research and Training Fellowship from the American Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M. and A.K. were supported in part by the UCLA-California State University Northridge CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and the Quantitative and Computational Biosciences Collaboratory community, directed by M. Pellegrini.","day":"23","isi":1,"author":[{"full_name":"Samarasinghe, Ranmal A.","last_name":"Samarasinghe","first_name":"Ranmal A."},{"first_name":"Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","full_name":"Miranda, Osvaldo"},{"first_name":"Jessie E.","last_name":"Buth","full_name":"Buth, Jessie E."},{"first_name":"Simon","last_name":"Mitchell","full_name":"Mitchell, Simon"},{"first_name":"Isabella","last_name":"Ferando","full_name":"Ferando, Isabella"},{"last_name":"Watanabe","first_name":"Momoko","full_name":"Watanabe, Momoko"},{"full_name":"Kurdian, Arinnae","first_name":"Arinnae","last_name":"Kurdian"},{"full_name":"Golshani, Peyman","last_name":"Golshani","first_name":"Peyman"},{"full_name":"Plath, Kathrin","last_name":"Plath","first_name":"Kathrin"},{"last_name":"Lowry","first_name":"William E.","full_name":"Lowry, William E."},{"first_name":"Jack M.","last_name":"Parent","full_name":"Parent, Jack M."},{"last_name":"Mody","first_name":"Istvan","full_name":"Mody, Istvan"},{"last_name":"Novitch","first_name":"Bennett G.","full_name":"Novitch, Bennett G."}],"main_file_link":[{"url":"https://doi.org/10.1038/s41593-021-00906-5","open_access":"1"}],"citation":{"apa":"Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe, M., … Novitch, B. G. (2021). <i>Identification of neural oscillations and epileptiform changes in human brain organoids</i> (Vol. 24). Springer Nature. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>","mla":"Samarasinghe, Ranmal A., et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol. 24, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>.","ista":"Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification of neural oscillations and epileptiform changes in human brain organoids, Springer Nature, 32p.","chicago":"Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol. 24. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>.","short":"R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe, A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch, Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids, Springer Nature, 2021.","ieee":"R. A. Samarasinghe <i>et al.</i>, <i>Identification of neural oscillations and epileptiform changes in human brain organoids</i>, vol. 24. Springer Nature, 2021.","ama":"Samarasinghe RA, Miranda O, Buth JE, et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol 24. Springer Nature; 2021. doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>"},"intvolume":"        24","doi":"10.1038/s41593-021-00906-5","publication_status":"published","oa_version":"Published Version","date_published":"2021-08-23T00:00:00Z","status":"public","oa":1,"publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"month":"08","abstract":[{"text":"Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.","lang":"eng"}],"date_updated":"2023-08-04T10:49:44Z","year":"2021","_id":"6995"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","publisher":"Cold Spring Harbor Laboratory","oa":1,"title":"TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids","month":"12","abstract":[{"lang":"eng","text":"Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGFβ superfamily signaling pathways and increased expression of genes associated with naïve pluripotency. We further identify combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling."}],"date_updated":"2022-06-17T08:03:32Z","year":"2019","extern":"1","day":"13","author":[{"first_name":"Momoko","last_name":"Watanabe","full_name":"Watanabe, Momoko"},{"full_name":"Haney, Jillian R.","first_name":"Jillian R.","last_name":"Haney"},{"full_name":"Vishlaghi, Neda","first_name":"Neda","last_name":"Vishlaghi"},{"first_name":"Felix","last_name":"Turcios","full_name":"Turcios, Felix"},{"last_name":"Buth","first_name":"Jessie E.","full_name":"Buth, Jessie E."},{"full_name":"Gu, Wen","first_name":"Wen","last_name":"Gu"},{"first_name":"Amanda J.","last_name":"Collier","full_name":"Collier, Amanda J."},{"full_name":"Miranda, Osvaldo","first_name":"Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425"},{"first_name":"Di","last_name":"Chen","full_name":"Chen, Di"},{"first_name":"Shan","last_name":"Sabri","full_name":"Sabri, Shan"},{"last_name":"Clark","first_name":"Amander T.","full_name":"Clark, Amander T."},{"first_name":"Kathrin","last_name":"Plath","full_name":"Plath, Kathrin"},{"first_name":"Heather R.","last_name":"Christofk","full_name":"Christofk, Heather R."},{"last_name":"Gandal","first_name":"Michael J.","full_name":"Gandal, Michael J."},{"first_name":"Bennett G.","last_name":"Novitch","full_name":"Novitch, Bennett G."}],"_id":"7358","article_processing_charge":"No","main_file_link":[{"url":"https://doi.org/10.1101/2019.12.13.875773","open_access":"1"}],"citation":{"ama":"Watanabe M, Haney JR, Vishlaghi N, et al. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. <i>bioRxiv</i>. 2019. doi:<a href=\"https://doi.org/10.1101/2019.12.13.875773\">10.1101/2019.12.13.875773</a>","ieee":"M. Watanabe <i>et al.</i>, “TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2019.","short":"M. Watanabe, J.R. Haney, N. Vishlaghi, F. Turcios, J.E. Buth, W. Gu, A.J. Collier, O. Miranda, D. Chen, S. Sabri, A.T. Clark, K. Plath, H.R. Christofk, M.J. Gandal, B.G. Novitch, BioRxiv (2019).","ista":"Watanabe M, Haney JR, Vishlaghi N, Turcios F, Buth JE, Gu W, Collier AJ, Miranda O, Chen D, Sabri S, Clark AT, Plath K, Christofk HR, Gandal MJ, Novitch BG. 2019. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. bioRxiv, <a href=\"https://doi.org/10.1101/2019.12.13.875773\">10.1101/2019.12.13.875773</a>.","apa":"Watanabe, M., Haney, J. R., Vishlaghi, N., Turcios, F., Buth, J. E., Gu, W., … Novitch, B. G. (2019). TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2019.12.13.875773\">https://doi.org/10.1101/2019.12.13.875773</a>","mla":"Watanabe, Momoko, et al. “TGFβ Superfamily Signaling Regulates the State of Human Stem Cell Pluripotency and Competency to Create Telencephalic Organoids.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2019, doi:<a href=\"https://doi.org/10.1101/2019.12.13.875773\">10.1101/2019.12.13.875773</a>.","chicago":"Watanabe, Momoko, Jillian R. Haney, Neda Vishlaghi, Felix Turcios, Jessie E. Buth, Wen Gu, Amanda J. Collier, et al. “TGFβ Superfamily Signaling Regulates the State of Human Stem Cell Pluripotency and Competency to Create Telencephalic Organoids.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2019. <a href=\"https://doi.org/10.1101/2019.12.13.875773\">https://doi.org/10.1101/2019.12.13.875773</a>."},"doi":"10.1101/2019.12.13.875773","publication_status":"published","publication":"bioRxiv","page":"75","date_created":"2020-01-23T09:53:40Z","oa_version":"Preprint","type":"preprint","date_published":"2019-12-13T00:00:00Z","language":[{"iso":"eng"}]}]