دورية أكاديمية

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

التفاصيل البيبلوغرافية
العنوان: An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients
المؤلفون: Jonathan Li, Ryan G. Lim, Julia A. Kaye, Victoria Dardov, Alyssa N. Coyne, Jie Wu, Pamela Milani, Andrew Cheng, Terri G. Thompson, Loren Ornelas, Aaron Frank, Miriam Adam, Maria G. Banuelos, Malcolm Casale, Veerle Cox, Renan Escalante-Chong, J. Gavin Daigle, Emilda Gomez, Lindsey Hayes, Ronald Holewenski, Susan Lei, Alex Lenail, Leandro Lima, Berhan Mandefro, Andrea Matlock, Lindsay Panther, Natasha Leanna Patel-Murray, Jacqueline Pham, Divya Ramamoorthy, Karen Sachs, Brandon Shelley, Jennifer Stocksdale, Hannah Trost, Mark Wilhelm, Vidya Venkatraman, Brook T. Wassie, Stacia Wyman, Stephanie Yang, Jennifer E. Van Eyk, Thomas E. Lloyd, Steven Finkbeiner, Ernest Fraenkel, Jeffrey D. Rothstein, Dhruv Sareen, Clive N. Svendsen, Leslie M. Thompson, Hemali Phatnani, PhD, Justin Kwan, MD, Dhruv Sareen, PhD, James R. Broach, PhD, Zachary Simmons, MD, Ximena Arcila-Londono, MD, Edward B. Lee, MD, PhD, Vivianna M. Van Deerlin, MD, PhD, Neil A. Shneider, MD, PhD, Ernest Fraenkel, PhD, Lyle W. Ostrow, MD, PhD, Frank Baas, MD, PhD, Noah Zaitlen, PhD, James D. Berry, MD, MPH, Andrea Malaspina, MD, PhD, Pietro Fratta, MD, PhD, Gregory A. Cox, PhD, Leslie M. Thompson, PhD, Steve Finkbeiner, MD, PhD, Efthimios Dardiotis, MD, PhD, Timothy M. Miller, MD, PhD, Siddharthan Chandran, PhD, Suvankar Pal, MD, Eran Hornstein, MD, PhD, Daniel J. MacGowan, MD, Terry Heiman-Patterson, MD, Molly G. Hammell, PhD, Nikolaos.A. Patsopoulos, MD, PhD, Oleg Butovsky, PhD, Joshua Dubnau, PhD, Avindra Nath, MD, Robert Bowser, PhD, Matt Harms, MD, Mary Poss, DVM, PhD, Jennifer Phillips-Cremins, PhD, John Crary, MD, PhD, Nazem Atassi, MD, Dale J. Lange, MD, Darius J. Adams, MD, Leonidas Stefanis, MD, PhD, Marc Gotkine, MD, Robert H. Baloh, MD. PhD, Suma Babu, MBBS, MPH, Towfique Raj, PhD, Sabrina Paganoni, MD, PhD, Ophir Shalem, PhD, Colin Smith, MD, Bin Zhang, PhD, Brent Harris, MD, PhD, Iris Broce, PhD, Vivian Drory, MD, John Ravits, MD, Corey McMillan, PhD, Vilas Menon, PhD, Lani Wu, PhD, Steven Altschuler, PhD
المصدر: iScience, Vol 24, Iss 11, Pp 103221- (2021)
بيانات النشر: Elsevier, 2021.
سنة النشر: 2021
المجموعة: LCC:Science
مصطلحات موضوعية: Biological sciences, Neuroscience, Systems neuroscience, Systems biology, Omics, Science
الوصف: Summary: Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2589-0042
العلاقة: http://www.sciencedirect.com/science/article/pii/S2589004221011895Test; https://doaj.org/toc/2589-0042Test
DOI: 10.1016/j.isci.2021.103221
الوصول الحر: https://doaj.org/article/b0aa201abf104ba08a6430dac01837c5Test
رقم الانضمام: edsdoj.b0aa201abf104ba08a6430dac01837c5
قاعدة البيانات: Directory of Open Access Journals
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Wassie ) ) ) [36] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Stacia Wyman ) ) ) [37] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Stephanie Yang ) ) ) [38] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Jennifer E. Van Eyk ) ) ) [39] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Thomas E. Lloyd ) ) ) [40] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Steven Finkbeiner ) ) ) [41] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ernest Fraenkel ) ) ) [42] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Jeffrey D. Rothstein ) ) ) [43] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Dhruv Sareen ) ) ) [44] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Clive N. Svendsen ) ) ) [45] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Leslie M. Thompson ) ) ) [46] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Hemali Phatnani, PhD ) ) ) [47] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Justin Kwan, MD ) ) ) [48] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Dhruv Sareen, PhD ) ) ) [49] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => James R. Broach, PhD ) ) ) [50] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Zachary Simmons, MD ) ) ) [51] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ximena Arcila-Londono, MD ) ) ) [52] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Edward B. Lee, MD, PhD ) ) ) [53] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Vivianna M. Van Deerlin, MD, PhD ) ) ) [54] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Neil A. Shneider, MD, PhD ) ) ) [55] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ernest Fraenkel, PhD ) ) ) [56] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Lyle W. Ostrow, MD, PhD ) ) ) [57] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Frank Baas, MD, PhD ) ) ) [58] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Noah Zaitlen, PhD ) ) ) [59] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => James D. Berry, MD, MPH ) ) ) [60] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Andrea Malaspina, MD, PhD ) ) ) [61] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Pietro Fratta, MD, PhD ) ) ) [62] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Gregory A. Cox, PhD ) ) ) [63] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Leslie M. Thompson, PhD ) ) ) [64] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Steve Finkbeiner, MD, PhD ) ) ) [65] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Efthimios Dardiotis, MD, PhD ) ) ) [66] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Timothy M. Miller, MD, PhD ) ) ) [67] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Siddharthan Chandran, PhD ) ) ) [68] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Suvankar Pal, MD ) ) ) [69] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Eran Hornstein, MD, PhD ) ) ) [70] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Daniel J. MacGowan, MD ) ) ) [71] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Terry Heiman-Patterson, MD ) ) ) [72] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Molly G. Hammell, PhD ) ) ) [73] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Nikolaos.A. Patsopoulos, MD, PhD ) ) ) [74] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Oleg Butovsky, PhD ) ) ) [75] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Joshua Dubnau, PhD ) ) ) [76] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Avindra Nath, MD ) ) ) [77] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Robert Bowser, PhD ) ) ) [78] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Matt Harms, MD ) ) ) [79] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Mary Poss, DVM, PhD ) ) ) [80] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Jennifer Phillips-Cremins, PhD ) ) ) [81] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => John Crary, MD, PhD ) ) ) [82] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Nazem Atassi, MD ) ) ) [83] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Dale J. 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PhD ) ) ) [88] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Suma Babu, MBBS, MPH ) ) ) [89] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Towfique Raj, PhD ) ) ) [90] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Sabrina Paganoni, MD, PhD ) ) ) [91] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ophir Shalem, PhD ) ) ) [92] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Colin Smith, MD ) ) ) [93] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Bin Zhang, PhD ) ) ) [94] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Brent Harris, MD, PhD ) ) ) [95] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Iris Broce, PhD ) ) ) [96] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Vivian Drory, MD ) ) ) [97] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => John Ravits, MD ) ) ) [98] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Corey McMillan, PhD ) ) ) [99] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Vilas Menon, PhD ) ) ) [100] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Lani Wu, PhD ) ) ) [101] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Steven Altschuler, PhD ) ) ) ) [IsPartOfRelationships] => Array ( [0] => Array ( [BibEntity] => Array ( [Dates] => Array ( [0] => Array ( [D] => 01 [M] => 11 [Type] => published [Y] => 2021 ) ) [Identifiers] => Array ( [0] => Array ( [Type] => issn-print [Value] => 25890042 ) ) [Numbering] => Array ( [0] => Array ( [Type] => volume [Value] => 24 ) [1] => Array ( [Type] => issue [Value] => 11 ) ) [Titles] => Array ( [0] => Array ( [TitleFull] => iScience [Type] => main ) ) ) ) ) ) )
IllustrationInfo