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Cited by 14Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research Studies

Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies

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Lanciotti, Angela, Brignone, Maria Stefania, Macioce, Pompeo, Visentin, Sergio, Ambrosini, Elena·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms23010274PMC PMC8745131
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Abstract

Astrocytes are very versatile cells, endowed with multitasking capacities to ensure brain homeostasis maintenance from brain development to adult life. It has become increasingly evident that astrocytes play a central role in many central nervous system pathologies, not only as regulators of defensive responses against brain insults but also as primary culprits of the disease onset and progression. This is particularly evident in some rare leukodystrophies (LDs) where white matter/myelin deterioration is due to primary astrocyte dysfunctions. Understanding the molecular defects causing these LDs may help clarify astrocyte contribution to myelin formation/maintenance and favor the identification of possible therapeutic targets for LDs and other CNS demyelinating diseases. To date, the pathogenic mechanisms of these LDs are poorly known due to the rarity of the pathological tissue and the failure of the animal models to fully recapitulate the human diseases. Thus, the development of human induced pluripotent stem cells (hiPSC) from patient fibroblasts and their differentiation into astrocytes is a promising approach to overcome these issues. In this review, we discuss the primary role of astrocytes in LD pathogenesis, the experimental models currently available and the advantages, future evolutions, perspectives, and limitations of hiPSC to study pathologies implying astrocyte dysfunctions.

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  • Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes.

    “Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes [345,406,480,481,482,483,484].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [482]

    Section 5 reports that iPSC-derived astrocytes acquire adult astrocyte genes and that a 3D model closely recapitulates aspects of in vivo astrocyte development. Section 3.2 reports disease-related defects in patient-derived iPSC astrocytes. The paper does not establish transcriptome-level similarity for both cell types or describe an iPSC microglia model capturing disease phenotypes; its disease examples concern rare leukodystrophies. (LLM, conf=0.85)

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  1. [2]Verkhratsky A. Nedergaard M. Physiology of Astroglia Physiol. Rev. 2018 98 239 389 10.1152/physrev.00042.2016 29351512 PMC6050349 · DOI · Paper page
  2. [3]Kettenmann H. Verkhratsky A. Neuroglia: The 150 Years After Trends Neurosci. 2008 31 653 659 10.1016/j.tins.2008.09.003 18945498 · DOI
  3. [4]Sofroniew M.V. Vinters H.V. Astrocytes: Biology and Pathology Acta Neuropathol. 2010 119 7 35 10.1007/s00401-009-0619-8 20012068 PMC2799634 · DOI · Paper page
  4. [5]Köhler S. Winkler U. Hirrlinger J. Heterogeneity of Astrocytes in Grey and White Matter Neurochem. Res. 2021 46 3 14 10.1007/s11064-019-02926-x 31797158 · DOI · Paper page
  5. [7]Abbott N.J. Patabendige A.A.K. Dolman D.E.M. Yusof S.R. Begley D.J. Structure and Function of the Blood-Brain Barrier Neurobiol. Dis. 2010 37 13 25 10.1016/j.nbd.2009.07.030 19664713 · DOI · Paper page
  6. [8]Gawdi R. Emmady P.D. Physiology, Blood Brain Barrier StatPearls StatPearls Publishing Treasure Island, FL, USA 2021 32491653
  7. [9]Archie S.R. Al Shoyaib A. Cucullo L. Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview Pharmaceutics 2021 13 1779 10.3390/pharmaceutics13111779 34834200 PMC8622070 · DOI
  8. [10]Kugler E.C. Greenwood J. MacDonald R.B. The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction Front. Cell Dev. Biol. 2021 9 732820 10.3389/fcell.2021.732820 34646826 PMC8502923 · DOI
  9. [11]Stackhouse T.L. Mishra A. Neurovascular Coupling in Development and Disease: Focus on Astrocytes Front Cell Dev. Biol. 2021 9 702832 10.3389/fcell.2021.702832 34327206 PMC8313501 · DOI
  10. [12]Scemes E. Giaume C. Astrocyte Calcium Waves: What They Are and What They Do Glia 2006 54 716 725 10.1002/glia.20374 17006900 PMC2605018 · DOI
  11. [13]Goldberg M. De Pittà M. Volman V. Berry H. Ben-Jacob E. Nonlinear Gap Junctions Enable Long-Distance Propagation of Pulsating Calcium Waves in Astrocyte Networks PLoS Comput. Biol. 2010 6 e1000909 10.1371/journal.pcbi.1000909 20865153 PMC2928752 · DOI
  12. [14]Jha M.K. Kim J.-H. Song G.J. Lee W.-H. Lee I.-K. Lee H.-W. An S.S.A. Kim S. Suk K. Functional Dissection of Astrocyte-Secreted Proteins: Implications in Brain Health and Diseases Prog. Neurobiol. 2018 162 37 69 10.1016/j.pneurobio.2017.12.003 29247683 · DOI
  13. [15]Hughes A.N. Glial Cells Promote Myelin Formation and Elimination Front. Cell Dev. Biol. 2021 9 661486 10.3389/fcell.2021.661486 34046407 PMC8144722 · DOI
  14. [16]Tan C.X. Burrus Lane C.J. Eroglu C. Role of Astrocytes in Synapse Formation and Maturation Curr. Top. Dev. Biol. 2021 142 371 407 10.1016/bs.ctdb.2020.12.010 33706922 · DOI
  15. [17]Han R.T. Kim R.D. Molofsky A.V. Liddelow S.A. Astrocyte-Immune Cell Interactions in Physiology and Pathology Immunity 2021 54 211 224 10.1016/j.immuni.2021.01.013 33567261 · DOI · Paper page
  16. [19]Liddelow S.A. Barres B.A. Reactive Astrocytes: Production, Function, and Therapeutic Potential Immunity 2017 46 957 967 10.1016/j.immuni.2017.06.006 28636962 · DOI · Paper page
  17. [20]Sofroniew M.V. Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity Trends Immunol. 2020 41 758 770 10.1016/j.it.2020.07.004 32819810 PMC7484257 · DOI · Paper page
  18. [21]Linnerbauer M. Rothhammer V. Protective Functions of Reactive Astrocytes Following Central Nervous System Insult Front Immunol. 2020 11 573256 10.3389/fimmu.2020.573256 33117368 PMC7561408 · DOI
  19. [22]Pekny M. Pekna M. Messing A. Steinhäuser C. Lee J.-M. Parpura V. Hol E.M. Sofroniew M.V. Verkhratsky A. Astrocytes: A Central Element in Neurological Diseases Acta Neuropathol. 2016 131 323 345 10.1007/s00401-015-1513-1 26671410 · DOI
  20. [23]Zhou Y. Shao A. Yao Y. Tu S. Deng Y. Zhang J. Dual Roles of Astrocytes in Plasticity and Reconstruction after Traumatic Brain Injury Cell Commun. Signal 2020 18 62 10.1186/s12964-020-00549-2 32293472 PMC7158016 · DOI
  21. [25]Wang P. Ye Y. Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy Life 2021 11 938 10.3390/life11090938 34575087 PMC8471224 · DOI
  22. [26]Reid J.K. Kuipers H.F. She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders Front. Cell. Neurosci. 2021 15 704884 10.3389/fncel.2021.704884 34539348 PMC8446364 · DOI
  23. [27]Valori C.F. Guidotti G. Brambilla L. Rossi D. Astrocytes: Emerging Therapeutic Targets in Neurological Disorders Trends Mol. Med. 2019 25 750 759 10.1016/j.molmed.2019.04.010 31122805 · DOI
  24. [28]Yu X. Nagai J. Khakh B.S. Improved Tools to Study Astrocytes Nat. Rev. Neurosci. 2020 21 121 138 10.1038/s41583-020-0264-8 32042146 · DOI · Paper page
  25. [29]Ravi K. Paidas M.J. Saad A. Jayakumar A.R. Astrocytes in Rare Neurological Conditions: Morphological and Functional Considerations J. Comp. Neurol. 2021 529 2676 2705 10.1002/cne.25118 33496339 · DOI
  26. [30]Reinhard C. Bachoud-Lévi A.-C. Bäumer T. Bertini E. Brunelle A. Buizer A.I. Federico A. Gasser T. Groeschel S. Hermanns S. The European Reference Network for Rare Neurological Diseases Front. Neurol. 2020 11 616569 10.3389/fneur.2020.616569 33519696 PMC7840612 · DOI
  27. [31]Rutherford H.A. Hamilton N. Animal Models of Leukodystrophy: A New Perspective for the Development of Therapies FEBS J. 2019 286 4176 4191 10.1111/febs.15060 31520449 · DOI
  28. [32]Trudler D. Ghatak S. Lipton S.A. Emerging HiPSC Models for Drug Discovery in Neurodegenerative Diseases Int. J. Mol. Sci. 2021 22 8196 10.3390/ijms22158196 34360966 PMC8347370 · DOI
  29. [33]Rutherford H.A. Kasher P.R. Hamilton N. Dirty Fish Versus Squeaky Clean Mice: Dissecting Interspecies Differences Between Animal Models of Interferonopathy Front. Immunol. 2020 11 623650 10.3389/fimmu.2020.623650 33519829 PMC7843416 · DOI
  30. [34]Zhang Y. Sloan S.A. Clarke L.E. Caneda C. Plaza C.A. Blumenthal P.D. Vogel H. Steinberg G.K. Edwards M.S.B. Li G. Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse Neuron 2016 89 37 53 10.1016/j.neuron.2015.11.013 26687838 PMC4707064 · DOI · Paper page
  31. [35]Matyash V. Kettenmann H. Heterogeneity in Astrocyte Morphology and Physiology Brain Res. Rev. 2010 63 2 10 10.1016/j.brainresrev.2009.12.001 20005253 · DOI
  32. [36]Tarassishin L. Suh H.-S. Lee S.C. LPS and IL-1 Differentially Activate Mouse and Human Astrocytes: Role of CD14 Glia 2014 62 999 1013 10.1002/glia.22657 24659539 PMC4015139 · DOI
  33. [37]Takahashi K. Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors Cell 2006 126 663 676 10.1016/j.cell.2006.07.024 16904174 · DOI · Paper page
  34. [38]Karagiannis P. Takahashi K. Saito M. Yoshida Y. Okita K. Watanabe A. Inoue H. Yamashita J.K. Todani M. Nakagawa M. Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development Physiol. Rev. 2019 99 79 114 10.1152/physrev.00039.2017 30328784 · DOI
  35. [39]Li L. Shi Y. When Glia Meet Induced Pluripotent Stem Cells (IPSCs) Mol. Cell Neurosci. 2020 109 103565 10.1016/j.mcn.2020.103565 33068719 PMC10506562 · DOI
  36. [40]Ren B. Dunaevsky A. Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells Int. J. Mol. Sci. 2021 22 1692 10.3390/ijms22041692 33567562 PMC7915337 · DOI
  37. [41]Albert K. Niskanen J. Kälvälä S. Lehtonen Š. Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia Int. J. Mol. Sci. 2021 22 4334 10.3390/ijms22094334 33919317 PMC8122303 · DOI
  38. [42]van der Knaap M.S. Schiffmann R. Mochel F. Wolf N.I. Diagnosis, Prognosis, and Treatment of Leukodystrophies Lancet Neurol. 2019 18 962 972 10.1016/S1474-4422(19)30143-7 31307818 · DOI · Paper page
  39. [43]Vanderver A. Prust M. Tonduti D. Mochel F. Hussey H.M. Helman G. Garbern J. Eichler F. Labauge P. Aubourg P. Case Definition and Classification of Leukodystrophies and Leukoencephalopathies Mol. Genet. Metab. 2015 114 494 500 10.1016/j.ymgme.2015.01.006 25649058 PMC4390457 · DOI
  40. [45]Ashrafi M.R. Amanat M. Garshasbi M. Kameli R. Nilipour Y. Heidari M. Rezaei Z. Tavasoli A.R. An Update on Clinical, Pathological, Diagnostic, and Therapeutic Perspectives of Childhood Leukodystrophies Expert Rev. Neurother. 2020 20 65 84 10.1080/14737175.2020.1699060 31829048 · DOI
  41. [46]Garcia L.M. Hacker J.L. Sase S. Adang L. Almad A. Glial Cells in the Driver Seat of Leukodystrophy Pathogenesis Neurobiol. Dis. 2020 146 105087 10.1016/j.nbd.2020.105087 32977022 · DOI
  42. [47]Urbik V.M. Schmiedel M. Soderholm H. Bonkowsky J.L. Expanded Phenotypic Definition Identifies Hundreds of Potential Causative Genes for Leukodystrophies and Leukoencephalopathies Child Neurol. Open 2020 7 2329048X2093900 10.1177/2329048X20939003 PMC7359642 32704519 · DOI
  43. [48]Nave K.-A. Myelination and Support of Axonal Integrity by Glia Nature 2010 468 244 252 10.1038/nature09614 21068833 · DOI · Paper page
  44. [49]Lundgaard I. Osório M.J. Kress B.T. Sanggaard S. Nedergaard M. White Matter Astrocytes in Health and Disease Neuroscience 2014 276 161 173 10.1016/j.neuroscience.2013.10.050 24231735 PMC4016995 · DOI
  45. [50]Rodriguez D. Leukodystrophies with Astrocytic Dysfunction Handb. Clin. Neurol. 2013 113 1619 1628 10.1016/B978-0-444-59565-2.00030-7 23622383 · DOI
  46. [51]Lanciotti A. Brignone M.S. Bertini E. Petrucci T.C. Aloisi F. Ambrosini E. Astrocytes: Emerging Stars in Leukodystrophy Pathogenesis Transl. Neurosci. 2013 4 10.2478/s13380-013-0118-1 PMC3856885 24340223 · DOI
  47. [52]De Waard D.M. Bugiani M. Astrocyte-Oligodendrocyte-Microglia Crosstalk in Astrocytopathies Front. Cell Neurosci. 2020 14 608073 10.3389/fncel.2020.608073 33328899 PMC7710860 · DOI
  48. [53]Barres B.A. The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease Neuron 2008 60 430 440 10.1016/j.neuron.2008.10.013 18995817 · DOI · Paper page
  49. [54]Parpura V. Verkhratsky A. Homeostatic Function of Astrocytes: Ca2+ and Na+ Signalling Transl. Neurosci. 2012 3 334 344 10.2478/s13380-012-0040-y 23243501 PMC3520132 · DOI
  50. [55]Krencik R. Weick J.P. Liu Y. Zhang Z.-J. Zhang S.-C. Specification of Transplantable Astroglial Subtypes from Human Pluripotent Stem Cells Nat. Biotechnol. 2011 29 528 534 10.1038/nbt.1877 21602806 PMC3111840 · DOI
  51. [56]Jones J.R. Kong L. Hanna M.G. Hoffman B. Krencik R. Bradley R. Hagemann T. Choi J. Doers M. Dubovis M. Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes Cell Rep. 2018 25 947 958.e4 10.1016/j.celrep.2018.09.083 30355500 PMC6275075 · DOI
  52. [58]Kondo T. Funayama M. Miyake M. Tsukita K. Era T. Osaka H. Ayaki T. Takahashi R. Inoue H. Modeling Alexander Disease with Patient IPSCs Reveals Cellular and Molecular Pathology of Astrocytes Acta Neuropathol. Commun. 2016 4 69 10.1186/s40478-016-0337-0 27402089 PMC4940830 · DOI
  53. [59]Krencik R. Zhang S.-C. Directed Differentiation of Functional Astroglial Subtypes from Human Pluripotent Stem Cells Nat. Protoc. 2011 6 1710 1717 10.1038/nprot.2011.405 22011653 PMC3198813 · DOI
  54. [60]Li L. Tian E. Chen X. Chao J. Klein J. Qu Q. Sun G. Sun G. Huang Y. Warden C.D. GFAP mutations in astrocytes impair oligodendrocyte progenitor proliferation and myelination in an HiPSC model of Alexander Disease Cell Stem Cell 2018 23 239 251.e6 10.1016/j.stem.2018.07.009 30075130 PMC6230521 · DOI
  55. [61]Canals I. Ginisty A. Quist E. Timmerman R. Fritze J. Miskinyte G. Monni E. Hansen M.G. Hidalgo I. Bryder D. Rapid and Efficient Induction of Functional Astrocytes from Human Pluripotent Stem Cells Nat. Methods 2018 15 693 696 10.1038/s41592-018-0103-2 30127505 · DOI
  56. [62]Nadadhur A.G. Leferink P.S. Holmes D. Hinz L. Cornelissen-Steijger P. Gasparotto L. Heine V.M. Patterning Factors during Neural Progenitor Induction Determine Regional Identity and Differentiation Potential in Vitro Stem Cell Res. 2018 32 25 34 10.1016/j.scr.2018.08.017 30172094 · DOI
  57. [63]Leferink P.S. Dooves S. Hillen A.E.J. Watanabe K. Jacobs G. Gasparotto L. Cornelissen-Steijger P. van der Knaap M.S. Heine V.M. Astrocyte Subtype Vulnerability in Stem Cell Models of Vanishing White Matter Ann. Neurol. 2019 86 780 792 10.1002/ana.25585 31433864 PMC6856690 · DOI
  58. [64]Zhou L. Li P. Chen N. Dai L. Gao K. Liu Y. Shen L. Wang J. Jiang Y. Wu Y. Modeling Vanishing White Matter Disease with Patient-derived Induced Pluripotent Stem Cells Reveals Astrocytic Dysfunction CNS Neurosci. Ther. 2019 25 759 771 10.1111/cns.13107 30720246 PMC6515702 · DOI
  59. [65]Yan Y. Shin S. Jha B.S. Liu Q. Sheng J. Li F. Zhan M. Davis J. Bharti K. Zeng X. Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells Stem Cells Transl. Med. 2013 2 862 870 10.5966/sctm.2013-0080 24113065 PMC3808201 · DOI
  60. [66]Griesi-Oliveira K. Acab A. Gupta A.R. Sunaga D.Y. Chailangkarn T. Nicol X. Nunez Y. Walker M.F. Murdoch J.D. Sanders S.J. Modeling Non-Syndromic Autism and the Impact of TRPC6 Disruption in Human Neurons Mol. Psychiatry 2015 20 1350 1365 10.1038/mp.2014.141 25385366 PMC4427554 · DOI · Paper page
  61. [68]Brenner M. Johnson A.B. Boespflug-Tanguy O. Rodriguez D. Goldman J.E. Messing A. Mutations in GFAP, Encoding Glial Fibrillary Acidic Protein, Are Associated with Alexander Disease Nat. Genet. 2001 27 117 120 10.1038/83679 11138011 · DOI
  62. [69]Hagemann T.L. Alexander Disease: Models, Mechanisms, and Medicine Curr. Opin. Neurobiol. 2021 72 140 147 10.1016/j.conb.2021.10.002 34826654 PMC8901527 · DOI
  63. [70]Prust M. Wang J. Morizono H. Messing A. Brenner M. Gordon E. Hartka T. Sokohl A. Schiffmann R. Gordish-Dressman H. GFAP Mutations, Age at Onset, and Clinical Subtypes in Alexander Disease Neurology 2011 77 1287 1294 10.1212/WNL.0b013e3182309f72 21917775 PMC3179649 · DOI
  64. [71]Nielsen A.L. Jørgensen P. Jørgensen A.L. Short Communication J. Neurogenet. 2002 16 175 179 10.1080/01677060215305 12696672 · DOI
  65. [72]Sosunov A. Olabarria M. Goldman J.E. Alexander Disease: An Astrocytopathy That Produces a Leukodystrophy Brain Pathol. 2018 28 388 398 10.1111/bpa.12601 29740945 PMC8028392 · DOI
  66. [73]Messing A. Brenner M. GFAP at 50 ASN Neuro 2020 12 175909142094968 10.1177/1759091420949680 32811163 PMC7440737 · DOI
  67. [74]Perng M.D. Su M. Wen S.F. Li R. Gibbon T. Prescott A.R. Brenner M. Quinlan R.A. The Alexander Disease–Causing Glial Fibrillary Acidic Protein Mutant, R416W, Accumulates into Rosenthal Fibers by a Pathway That Involves Filament Aggregation and the Association of αβ-Crystallin and HSP27 Am. J. Hum. Genet. 2006 79 197 213 10.1086/504411 16826512 PMC1559481 · DOI
  68. [75]Wang L. Hagemann T.L. Kalwa H. Michel T. Messing A. Feany M.B. Nitric Oxide Mediates Glial-Induced Neurodegeneration in Alexander Disease Nat. Commun. 2015 6 8966 10.1038/ncomms9966 26608817 PMC4674772 · DOI
  69. [76]Sprenkle N.T. Sims S.G. Sánchez C.L. Meares G.P. Endoplasmic Reticulum Stress and Inflammation in the Central Nervous System Mol. Neurodegener. 2017 12 42 10.1186/s13024-017-0183-y 28545479 PMC5445486 · DOI
  70. [77]Hagemann T.L. Connor J.X. Messing A. Alexander Disease-Associated Glial Fibrillary Acidic Protein Mutations in Mice Induce Rosenthal Fiber Formation and a White Matter Stress Response J. Neurosci. 2006 26 11162 11173 10.1523/JNEUROSCI.3260-06.2006 17065456 PMC6674663 · DOI
  71. [78]Olabarria M. Putilina M. Riemer E.C. Goldman J.E. Astrocyte Pathology in Alexander Disease Causes a Marked Inflammatory Environment Acta Neuropathol. 2015 130 469 486 10.1007/s00401-015-1469-1 26296699 · DOI
  72. [79]Heaven M.R. Herren A.W. Flint D.L. Pacheco N.L. Li J. Tang A. Khan F. Goldman J.E. Phinney B.S. Olsen M.L. Metabolic Enzyme Alterations and Astrocyte Dysfunction in a Murine Model of Alexander Disease with Severe Reactive Gliosis Mol. Cell. Proteom. 2021 21 100180 10.1016/j.mcpro.2021.100180 PMC8717607 34808356 · DOI
  73. [80]Candiani S. Carestiato S. Mack A.F. Bani D. Bozzo M. Obino V. Ori M. Rosamilia F. De Sarlo M. Pestarino M. Alexander Disease Modeling in Zebrafish: An In Vivo System Suitable to Perform Drug Screening Genes 2020 11 1490 10.3390/genes11121490 PMC7764705 33322348 · DOI
  74. [81]Lee S.H. Nam T.S. Kim K.H. Kim J.H. Yoon W. Heo S.H. Kim M.J. Shin B.A. Perng M.D. Choy H.E. Aggregation-prone GFAP mutation in Alexander disease validated using a zebrafish model BMC Neurol. 2017 17 175 10.1186/s12883-017-0938-7 28882119 PMC5590178 · DOI
  75. [82]Battaglia R.A. Beltran A.S. Delic S. Dumitru R. Robinson J.A. Kabiraj P. Herring L.E. Madden V.J. Ravinder N. Willems E. Site-Specific Phosphorylation and Caspase Cleavage of GFAP Are New Markers of Alexander Disease Severity eLife 2019 8 e47789 10.7554/eLife.47789 31682229 PMC6927689 · DOI
  76. [84]van der Knaap M.S. Barth P.G. Vrensen G.F.J.M. Valk J. Histopathology of an Infantile-Onset Spongiform Leukoencephalopathy with a Discrepantly Mild Clinical Course Acta Neuropathol. 1996 92 206 212 10.1007/s004010050510 8841668 · DOI
  77. [85]Leegwater P.A.J. Yuan B.Q. van der Steen J. Mulders J. Könst A.A.M. Boor P.K.I. Mejaski-Bosnjak V. van der Maarel S.M. Frants R.R. Oudejans C.B.M. Mutations of MLC1 (KIAA0027), Encoding a Putative Membrane Protein, Cause Megalencephalic Leukoencephalopathy with Subcortical Cysts Am. J. Hum. Genet. 2001 68 831 838 10.1086/319519 11254442 PMC1275636 · DOI
  78. [86]Duarri A. Lopez de Heredia M. Capdevila-Nortes X. Ridder M.C. Montolio M. López-Hernández T. Boor I. Lien C.-F. Hagemann T. Messing A. Knockdown of MLC1 in Primary Astrocytes Causes Cell Vacuolation: A MLC Disease Cell Model Neurobiol. Dis. 2011 43 228 238 10.1016/j.nbd.2011.03.015 21440627 PMC3885813 · DOI
  79. [87]Pascual-Castroviejo I. van der Knaap M.S. Pronk J.C. García-Segura J.M. Gutiérrez-Molina M. Pascual-Pascual S.I. Vacuolating Megalencephalic Leukoencephalopathy: 24 Year Follow-up of Two Siblings Neurologia 2005 20 33 40 15704020
  80. [88]López-Hernández T. Ridder M.C. Montolio M. Capdevila-Nortes X. Polder E. Sirisi S. Duarri A. Schulte U. Fakler B. Nunes V. Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism Am. J. Hum. Genet. 2011 88 422 432 10.1016/j.ajhg.2011.02.009 21419380 PMC3071909 · DOI
  81. [89]Teijido O. Martínez A. Pusch M. Zorzano A. Soriano E. del Río J.A. Palacín M. Estévez R. Localization and Functional Analyses of the MLC1 Protein Involved in Megalencephalic Leukoencephalopathy with Subcortical Cysts Hum. Mol. Genet. 2004 13 2581 2594 10.1093/hmg/ddh291 15367490 · DOI
  82. [90]López-Hernández T. Sirisi S. Capdevila-Nortes X. Montolio M. Fernández-Dueñas V. Scheper G.C. van der Knaap M.S. Casquero P. Ciruela F. Ferrer I. Molecular Mechanisms of MLC1 and GLIALCAM Mutations in Megalencephalic Leukoencephalopathy with Subcortical Cysts Hum. Mol. Genet. 2011 20 3266 3277 10.1093/hmg/ddr238 21624973 · DOI
  83. [91]Hamilton E.M.C. Tekturk P. Cialdella F. van Rappard D.F. Wolf N.I. Yalcinkaya C. Çetinçelik Ü. Rajaee A. Kariminejad A. Paprocka J. Megalencephalic Leukoencephalopathy with Subcortical Cysts: Characterization of Disease Variants Neurology 2018 90 e1395 e1403 10.1212/WNL.0000000000005334 29661901 PMC5902784 · DOI
  84. [92]Hoegg-Beiler M.B. Sirisi S. Orozco I.J. Ferrer I. Hohensee S. Auberson M. Gödde K. Vilches C. de Heredia M.L. Nunes V. Disrupting MLC1 and GlialCAM and ClC-2 Interactions in Leukodystrophy Entails Glial Chloride Channel Dysfunction Nat. Commun. 2014 5 3475 10.1038/ncomms4475 24647135 · DOI
  85. [93]Dubey M. Bugiani M. Ridder M.C. Postma N.L. Brouwers E. Polder E. Jacobs J.G. Baayen J.C. Klooster J. Kamermans M. Mice with Megalencephalic Leukoencephalopathy with Cysts: A Developmental Angle: MLC in Mouse and Man Ann. Neurol. 2015 77 114 131 10.1002/ana.24307 25382142 · DOI
  86. [94]Sugio S. Tohyama K. Oku S. Fujiyoshi K. Yoshimura T. Hikishima K. Yano R. Fukuda T. Nakamura M. Okano H. Astrocyte-Mediated Infantile-Onset Leukoencephalopathy Mouse Model: Infantile-Onset Leukoencephalopathy Model Glia 2017 65 150 168 10.1002/glia.23084 27748972 · DOI
  87. [95]Bugiani M. Dubey M. Breur M. Postma N.L. Dekker M.P. ter Braak T. Boschert U. Abbink T.E.M. Mansvelder H.D. Min R. Megalencephalic Leukoencephalopathy with Cysts: The Glialcam -Null Mouse Model Ann. Clin. Transl. Neurol. 2017 4 450 465 10.1002/acn3.405 28695146 PMC5497535 · DOI
  88. [96]Shi Z. Yan H.-F. Cao B.-B. Guo M.-M. Xie H. Gao K. Xiao J.-X. Yang Y.-L. Xiong H. Gu Q. Identification in Chinese Patients with GLIALCAM Mutations of Megalencephalic Leukoencephalopathy with Subcortical Cysts and Brain Pathological Study on Glialcam Knock-in Mouse Models World J. Pediatr. 2019 15 454 464 10.1007/s12519-019-00284-w 31372844 PMC6785595 · DOI
  89. [97]Pérez-Rius C. Folgueira M. Elorza-Vidal X. Alia A. Hoegg-Beiler M.B. Eeza M.N.H. Díaz M.L. Nunes V. Barrallo-Gimeno A. Estévez R. Comparison of Zebrafish and Mice Knockouts for Megalencephalic Leukoencephalopathy Proteins Indicates That GlialCAM/MLC1 Forms a Functional Unit Orphanet J. Rare Dis. 2019 14 268 10.1186/s13023-019-1248-5 31752924 PMC6873532 · DOI
  90. [98]Sirisi S. Folgueira M. López-Hernández T. Minieri L. Pérez-Rius C. Gaitán-Peñas H. Zang J. Martínez A. Capdevila-Nortes X. De La Villa P. Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein 1 Regulates Glial Surface Localization of GLIALCAM from Fish to Humans Hum. Mol. Genet. 2014 23 5069 5086 10.1093/hmg/ddu231 24824219 · DOI
  91. [99]Bosch A. Estévez R. Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy Front. Cell. Neurosci. 2021 14 627887 10.3389/fncel.2020.627887 33551753 PMC7862579 · DOI
  92. [100]Gilbert A. Elorza-Vidal X. Rancillac A. Chagnot A. Yetim M. Hingot V. Deffieux T. Boulay A.-C. Alvear-Perez R. Cisternino S. Megalencephalic Leukoencephalopathy with Subcortical Cysts Is a Developmental Disorder of the Gliovascular Unit eLife 2021 10 e71379 10.7554/eLife.71379 34723793 PMC8598235 · DOI
  93. [101]Brignone M.S. Lanciotti A. Macioce P. Macchia G. Gaetani M. Aloisi F. Petrucci T.C. Ambrosini E. The Beta1 Subunit of the Na,K-ATPase Pump Interacts with Megalencephalic Leucoencephalopathy with Subcortical Cysts Protein 1 (MLC1) in Brain Astrocytes: New Insights into MLC Pathogenesis Hum. Mol. Genet. 2011 20 90 103 10.1093/hmg/ddq435 20926452 PMC3000678 · DOI
  94. [102]Brignone M.S. Lanciotti A. Visentin S. De Nuccio C. Molinari P. Camerini S. Diociaiuti M. Petrini S. Minnone G. Crescenzi M. Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 Modulates Endosomal PH and Protein Trafficking in Astrocytes: Relevance to MLC Disease Pathogenesis Neurobiol. Dis. 2014 66 1 18 10.1016/j.nbd.2014.02.003 24561067 PMC4003525 · DOI
  95. [103]Lanciotti A. Brignone M.S. Camerini S. Serafini B. Macchia G. Raggi C. Molinari P. Crescenzi M. Musumeci M. Sargiacomo M. MLC1 Trafficking and Membrane Expression in Astrocytes: Role of Caveolin-1 and Phosphorylation Neurobiol. Dis. 2010 37 581 595 10.1016/j.nbd.2009.11.008 19931615 · DOI
  96. [104]Lanciotti A. Brignone M.S. Molinari P. Visentin S. De Nuccio C. Macchia G. Aiello C. Bertini E. Aloisi F. Petrucci T.C. Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein 1 Functionally Cooperates with the TRPV4 Cation Channel to Activate the Response of Astrocytes to Osmotic Stress: Dysregulation by Pathological Mutations Hum. Mol. Genet. 2012 21 2166 2180 10.1093/hmg/dds032 22328087 · DOI
  97. [105]Lanciotti A. Brignone M.S. Belfiore M. Columba-Cabezas S. Mallozzi C. Vincentini O. Molinari P. Petrucci T.C. Visentin S. Ambrosini E. Megalencephalic Leukoencephalopathy with Subcortical Cysts Disease-Linked MLC1 Protein Favors Gap-Junction Intercellular Communication by Regulating Connexin 43 Trafficking in Astrocytes Cells 2020 9 1425 10.3390/cells9061425 PMC7348769 32521795 · DOI
  98. [106]Wu M. Moh M.C. Schwarz H. HepaCAM Associates with Connexin 43 and Enhances Its Localization in Cellular Junctions Sci. Rep. 2016 6 36218 10.1038/srep36218 27819278 PMC5098153 · DOI
  99. [107]Elorza-Vidal X. Sirisi S. Gaitán-Peñas H. Pérez-Rius C. Alonso-Gardón M. Armand-Ugón M. Lanciotti A. Brignone M.S. Prat E. Nunes V. GlialCAM/MLC1 Modulates LRRC8/VRAC Currents in an Indirect Manner: Implications for Megalencephalic Leukoencephalopathy Neurobiol. Dis. 2018 119 88 99 10.1016/j.nbd.2018.07.031 30076890 · DOI
  100. [108]Ridder M.C. Boor I. Lodder J.C. Postma N.L. Capdevila-Nortes X. Duarri A. Brussaard A.B. Estévez R. Scheper G.C. Mansvelder H.D. Megalencephalic Leucoencephalopathy with Cysts: Defect in Chloride Currents and Cell Volume Regulation Brain 2011 134 3342 3354 10.1093/brain/awr255 22006981 · DOI
  101. [109]Van der Knaap M.S. Boor I. Estévez R. Megalencephalic Leukoencephalopathy with Subcortical Cysts: Chronic White Matter Oedema Due to a Defect in Brain Ion and Water Homoeostasis Lancet Neurol. 2012 11 973 985 10.1016/S1474-4422(12)70192-8 23079554 · DOI
  102. [110]Dubey M. Brouwers E. Hamilton E.M.C. Stiedl O. Bugiani M. Koch H. Kole M.H.P. Boschert U. Wykes R.C. Mansvelder H.D. Seizures and Disturbed Brain Potassium Dynamics in the Leukodystrophy Megalencephalic Leukoencephalopathy with Subcortical Cysts: Seizures in the Leukodystrophy MLC Ann. Neurol. 2018 83 636 649 10.1002/ana.25190 29466841 PMC5900999 · DOI
  103. [111]Lanciotti A. Brignone M.S. Visentin S. De Nuccio C. Catacuzzeno L. Mallozzi C. Petrini S. Caramia M. Veroni C. Minnone G. Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 Regulates Epidermal Growth Factor Receptor Signaling in Astrocytes Hum. Mol. Genet. 2016 25 1543 1558 10.1093/hmg/ddw032 26908604 · DOI
  104. [112]Brignone M.S. Lanciotti A. Serafini B. Mallozzi C. Sbriccoli M. Veroni C. Molinari P. Elorza-Vidal X. Petrucci T.C. Estévez R. Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 (MLC1) Counteracts Astrocyte Activation in Response to Inflammatory Signals Mol. Neurobiol. 2019 56 8237 8254 10.1007/s12035-019-01657-y 31209783 · DOI
  105. [113]Hwang J. Vu H.M. Kim M.-S. Lim H.-H. Plasma Membrane Localization of MLC1 Regulates Cellular Morphology and Motility Mol. Brain 2019 12 116 10.1186/s13041-019-0540-6 31888684 PMC6938022 · DOI
  106. [114]Van der Knaap M.S. Breiter S.N. Naidu S. Hart A.A. Valk J. Defining and Categorizing Leukoencephalopathies of Unknown Origin: MR Imaging Approach Radiology 1999 213 121 133 10.1148/radiology.213.1.r99se01121 10540652 · DOI
  107. [115]Van der Knaap M.S. Pronk J.C. Scheper G.C. Vanishing White Matter Disease Lancet Neurol. 2006 5 413 423 10.1016/S1474-4422(06)70440-9 16632312 · DOI
  108. [116]Bugiani M. Vuong C. Breur M. van der Knaap M.S. Vanishing White Matter: A Leukodystrophy Due to Astrocytic Dysfunction Brain Pathol. 2018 28 408 421 10.1111/bpa.12606 29740943 PMC8028328 · DOI
  109. [117]Van der Knaap M.S. Salomons G.S. Li R. Franzoni E. Gutiérrez-Solana L.G. Smit L.M.E. Robinson R. Ferrie C.D. Cree B. Reddy A. Unusual Variants of Alexander’s Disease: Atypical Alexander’s Disease Ann. Neurol. 2005 57 327 338 10.1002/ana.20381 15732098 · DOI
  110. [118]van der Knaap M.S. Kamphorst W. Barth P.G. Kraaijeveld C.L. Gut E. Valk J. Phenotypic Variation in Leukoencephalopathy with Vanishing White Matter Neurology 1998 51 540 547 10.1212/WNL.51.2.540 9710032 · DOI
  111. [119]Stellingwerff M.D. Al-Saady M.L. van de Brug T. Barkhof F. Pouwels P.J.W. van der Knaap M.S. MRI Natural History of the Leukodystrophy Vanishing White Matter Radiology 2021 300 671 680 10.1148/radiol.2021210110 34184934 · DOI
  112. [120]Leegwater P.A. Vermeulen G. Könst A.A. Naidu S. Mulders J. Visser A. Kersbergen P. Mobach D. Fonds D. van Berkel C.G. Subunits of the Translation Initiation Factor EIF2B Are Mutant in Leukoencephalopathy with Vanishing White Matter Nat. Genet. 2001 29 383 388 10.1038/ng764 11704758 · DOI
  113. [121]Shimada S. Shimojima K. Sangu N. Hoshino A. Hachiya Y. Ohto T. Hashi Y. Nishida K. Mitani M. Kinjo S. Mutations in the Genes Encoding Eukaryotic Translation Initiation Factor 2B in Japanese Patients with Vanishing White Matter Disease Brain Dev. 2015 37 960 966 10.1016/j.braindev.2015.03.003 25843247 · DOI
  114. [122]Pavitt G.D. EIF2B, a Mediator of General and Gene-Specific Translational Control Biochem. Soc. Trans. 2005 33 1487 1492 10.1042/BST0331487 16246152 · DOI
  115. [123]Pakos-Zebrucka K. Koryga I. Mnich K. Ljujic M. Samali A. Gorman A.M. The Integrated Stress Response EMBO Rep. 2016 17 1374 1395 10.15252/embr.201642195 27629041 PMC5048378 · DOI · Paper page
  116. [124]Dietrich J. Lacagnina M. Gass D. Richfield E. Mayer-Pröschel M. Noble M. Torres C. Pröschel C. EIF2B5 Mutations Compromise GFAP+ Astrocyte Generation in Vanishing White Matter Leukodystrophy Nat. Med. 2005 11 277 283 10.1038/nm1195 15723074 · DOI
  117. [125]Bugiani M. Boor I. Powers J.M. Scheper G.C. van der Knaap M.S. Leukoencephalopathy With Vanishing White Matter: A Review J. Neuropathol. Exp. Neurol. 2010 69 987 996 10.1097/NEN.0b013e3181f2eafa 20838246 · DOI · Paper page
  118. [126]Geva M. Cabilly Y. Assaf Y. Mindroul N. Marom L. Raini G. Pinchasi D. Elroy-Stein O. A Mouse Model for Eukaryotic Translation Initiation Factor 2B-Leucodystrophy Reveals Abnormal Development of Brain White Matter Brain 2010 133 2448 2461 10.1093/brain/awq180 20826436 · DOI
  119. [127]Dooves S. Bugiani M. Postma N.L. Polder E. Land N. Horan S.T. van Deijk A.-L.F. van de Kreeke A. Jacobs G. Vuong C. Astrocytes Are Central in the Pathomechanisms of Vanishing White Matter J. Clin. Investig. 2016 126 1512 1524 10.1172/JCI83908 26974157 PMC4811153 · DOI
  120. [128]Wisse L.E. Ter Braak T.J. van de Beek M.-C. van Berkel C.G.M. Wortel J. Heine V.M. Proud C.G. van der Knaap M.S. Abbink T.E.M. Adult Mouse EIF2Bε Arg191His Astrocytes Display a Normal Integrated Stress Response in Vitro Sci. Rep. 2018 8 3773 10.1038/s41598-018-21885-x 29491431 PMC5830650 · DOI
  121. [129]Herrero M. Daw M. Atzmon A. Elroy-Stein O. The Energy Status of Astrocytes Is the Achilles’ Heel of EIF2B-Leukodystrophy Cells 2021 10 1858 10.3390/cells10081858 34440627 PMC8393801 · DOI
  122. [130]Terumitsu-Tsujita M. Kitaura H. Miura I. Kiyama Y. Goto F. Muraki Y. Ominato S. Hara N. Simankova A. Bizen N. Glial Pathology in a Novel Spontaneous Mutant Mouse of the Eif2b5 Gene: A Vanishing White Matter Disease Model J. Neurochem. 2020 154 25 40 10.1111/jnc.14887 31587290 · DOI
  123. [131]Kim D. Lee Y.-R. Choi T.-I. Kim S.-H. Kang H.-C. Kim C.-H. Lee S. Comparative Proteome Research in a Zebrafish Model for Vanishing White Matter Disease Int. J. Mol. Sci. 2021 22 2707 10.3390/ijms22052707 33800130 PMC7962458 · DOI
  124. [132]Lee Y.-R. Kim S.H. Ben-Mahmoud A. Kim O.-H. Choi T.-I. Lee K.-H. Ku B. Eum J. Kee Y. Lee S. Eif2b3 Mutants Recapitulate Phenotypes of Vanishing White Matter Disease and Validate Novel Disease Alleles in Zebrafish Hum. Mol. Genet. 2021 30 331 342 10.1093/hmg/ddab033 33517449 · DOI
  125. [133]Keefe M.D. Soderholm H.E. Shih H.-Y. Stevenson T.J. Glaittli K.A. Bowles D.M. Scholl E. Colby S. Merchant S. Hsu E.W. Vanishing White Matter Disease Expression of Truncated EIF2B5 Activates Induced Stress Response elife 2020 9 e56319 10.7554/eLife.56319 33300869 PMC7752137 · DOI
  126. [134]Abbink T.E.M. Wisse L.E. Jaku E. Thiecke M.J. Voltolini-González D. Fritsen H. Bobeldijk S. Braak T.J. Polder E. Postma N.L. Vanishing White Matter: Deregulated Integrated Stress Response as Therapy Target Ann. Clin. Transl. Neurol. 2019 6 1407 1422 10.1002/acn3.50826 31402619 PMC6689685 · DOI
  127. [135]Cabilly Y. Barbi M. Geva M. Marom L. Chetrit D. Ehrlich M. Elroy-Stein O. Poor Cerebral Inflammatory Response in EIF2B Knock-In Mice: Implications for the Aetiology of Vanishing White Matter Disease PLoS ONE 2012 7 e46715 10.1371/journal.pone.0046715 23056417 PMC3464276 · DOI
  128. [136]Crow Y.J. Aicardi–Goutières Syndrome Handbook of Clinical Neurology Elsevier Amsterdam, The Netherlands 2013 Volume 113 1629 1635 978-0-444-59565-2 23622384
  129. [137]Livingston J. Crow Y. Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi–Goutières Syndrome and Beyond Neuropediatrics 2016 47 355 360 10.1055/s-0036-1592307 27643693 · DOI
  130. [138]Rice G. Patrick T. Parmar R. Taylor C.F. Aeby A. Aicardi J. Artuch R. Montalto S.A. Bacino C.A. Barroso B. Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome Am. J. Hum. Genet. 2007 81 713 725 10.1086/521373 17846997 PMC2227922 · DOI
  131. [139]Rice G.I. Kasher P.R. Forte G.M.A. Mannion N.M. Greenwood S.M. Szynkiewicz M. Dickerson J.E. Bhaskar S.S. Zampini M. Briggs T.A. Mutations in ADAR1 Cause Aicardi-Goutières Syndrome Associated with a Type I Interferon Signature Nat. Genet. 2012 44 1243 1248 10.1038/ng.2414 23001123 PMC4154508 · DOI · Paper page
  132. [140]Rice G.I. Del Toro Duany Y. Jenkinson E.M. Forte G.M. Anderson B.H. Ariaudo G. Bader-Meunier B. Baildam E.M. Battini R. Beresford M.W. Gain-of-Function Mutations in IFIH1 Cause a Spectrum of Human Disease Phenotypes Associated with Upregulated Type I Interferon Signaling Nat. Genet. 2014 46 503 509 10.1038/ng.2933 24686847 PMC4004585 · DOI
  133. [141]Goutières F. Aicardi-Goutières Syndrome Brain Dev. 2005 27 201 206 10.1016/j.braindev.2003.12.011 15737701 · DOI
  134. [142]Sase S. Takanohashi A. Vanderver A. Almad A. Astrocytes, an Active Player in Aicardi-Goutières Syndrome Brain Pathol. 2018 28 399 407 10.1111/bpa.12600 29740948 PMC8028286 · DOI
  135. [143]Onizawa H. Kato H. Kimura H. Kudo T. Soda N. Shimizu S. Funabiki M. Yagi Y. Nakamoto Y. Priller J. Aicardi–Goutières Syndrome-like Encephalitis in Mutant Mice with Constitutively Active MDA5 Int. Immunol. 2021 33 225 240 10.1093/intimm/dxaa073 33165593 · DOI
  136. [144]Genova E. Cavion F. Lucafò M. Pelin M. Lanzi G. Masneri S. Ferraro R.M. Fazzi E.M. Orcesi S. Decorti G. Biomarkers and Precision Therapy for Primary Immunodeficiencies: An In Vitro Study Based on Induced Pluripotent Stem Cells From Patients Clin. Pharmacol. Ther. 2020 108 358 367 10.1002/cpt.1837 32243572 · DOI
  137. [145]Ferraro R.M. Lanzi G. Masneri S. Barisani C. Piovani G. Savio G. Cattalini M. Galli J. Cereda C. Muzi-Falconi M. Generation of Three IPSC Lines from Fibroblasts of a Patient with Aicardi Goutières Syndrome Mutated in TREX1 Stem Cell Res. 2019 41 101580 10.1016/j.scr.2019.101580 31644995 · DOI
  138. [146]Ferraro R.M. Masneri S. Lanzi G. Barisani C. Piovani G. Savio G. Cattalini M. Galli J. Cereda C. Muzi-Falconi M. Establishment of Three IPSC Lines from Fibroblasts of a Patient with Aicardi Goutières Syndrome Mutated in RNaseH2B Stem Cell Res. 2019 41 101620 10.1016/j.scr.2019.101620 31678772 · DOI
  139. [147]Masneri S. Lanzi G. Ferraro R.M. Barisani C. Piovani G. Savio G. Cattalini M. Galli J. Cereda C. Muzi-Falconi M. Generation of Three Isogenic Induced Pluripotent Stem Cell Lines (IPSCs) from Fibroblasts of a Patient with Aicardi Goutières Syndrome Carrying a c.2471G>A Dominant Mutation in IFIH1 Gene Stem Cell Res. 2019 41 101623 10.1016/j.scr.2019.101623 31698194 · DOI
  140. [148]Fuchs N.V. Schieck M. Neuenkirch M. Tondera C. Schmitz H. Wendeburg L. Steinemann D. Elpers C. Rutsch F. König R. Generation of Three Induced Pluripotent eDeletion in the Genomic Locus of the Sterile Alpha Motif and HD Domain Containing Protein 1 (SAMHD1) Stem Cell Res. 2020 43 101697 10.1016/j.scr.2019.101697 32062129 · DOI
  141. [149]Depienne C. Bugiani M. Dupuits C. Galanaud D. Touitou V. Postma N. van Berkel C. Polder E. Tollard E. Darios F. Brain White Matter Oedema Due to ClC-2 Chloride Channel Deficiency: An Observational Analytical Study Lancet Neurol. 2013 12 659 668 10.1016/S1474-4422(13)70053-X 23707145 · DOI
  142. [150]Poroca D.R. Pelis R.M. Chappe V.M. ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies Front. Pharmacol. 2017 8 151 10.3389/fphar.2017.00151 28386229 PMC5362633 · DOI
  143. [151]Jentsch T.J. Pusch M. CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease Physiol. Rev. 2018 98 1493 1590 10.1152/physrev.00047.2017 29845874 · DOI
  144. [152]Elorza-Vidal X. Gaitán-Peñas H. Estévez R. Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease Int. J. Mol. Sci. 2019 20 1034 10.3390/ijms20051034 PMC6429410 30818802 · DOI
  145. [153]Blanz J. Schweizer M. Auberson M. Maier H. Muenscher A. Hubner C.A. Jentsch T.J. Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2 J. Neurosci. 2007 27 6581 6589 10.1523/JNEUROSCI.0338-07.2007 17567819 PMC6672451 · DOI
  146. [154]Göppner C. Soria A.H. Hoegg-Beiler M.B. Jentsch T.J. Cellular Basis of ClC-2 Cl− Channel–Related Brain and Testis Pathologies J. Biol. Chem. 2021 296 100074 10.1074/jbc.RA120.016031 33187987 PMC7949093 · DOI
  147. [155]Göppner C. Orozco I.J. Hoegg-Beiler M.B. Soria A.H. Hübner C.A. Fernandes-Rosa F.L. Boulkroun S. Zennaro M.C. Jentsch T.J. Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism Nat. Commun. 2019 10 4678 10.1038/s41467-019-12113-9 31615979 PMC6794291 · DOI
  148. [156]Akita H. Yoshie S. Ishida T. Takeishi Y. Hazama A. Negative chronotropic and inotropic effects of lubiprostone on iPS cell-derived cardiomyocytes via activation of CFTR BMC Complement. Med. Ther. 2020 20 118 10.1186/s12906-020-02923-6 32306956 PMC7169008 · DOI
  149. [157]Laird D.W. Life Cycle of Connexins in Health and Disease Biochem. J. 2006 394 527 543 10.1042/BJ20051922 16492141 PMC1383703 · DOI
  150. [158]Furuta N. Ikeda M. Hirayanagi K. Fujita Y. Amanuma M. Okamoto K. A Novel GJA1 Mutation in Oculodentodigital Dysplasia with Progressive Spastic Paraplegia and Sensory Deficits Intern. Med. 2012 51 93 98 10.2169/internalmedicine.51.5770 22214631 · DOI
  151. [159]Loddenkemper T. Grote K. Evers S. Oelerich M. Stögbauer F. Neurological Manifestations of the Oculodentodigital Dysplasia Syndrome J. Neurol. 2002 249 584 595 10.1007/s004150200068 12021949 · DOI
  152. [160]Saint-Val L. Courtin T. Charles P. Verny C. Catala M. Schiffmann R. Boespflug-Tanguy O. Mochel F. GJA1 Variants Cause Spastic Paraplegia Associated with Cerebral Hypomyelination AJNR Am. J. Neuroradiol. 2019 40 788 791 10.3174/ajnr.A6036 31023660 PMC7053899 · DOI
  153. [161]Gautier H.O.B. Evans K.A. Volbracht K. James R. Sitnikov S. Lundgaard I. James F. Lao-Peregrin C. Reynolds R. Franklin R.J.M. Neuronal Activity Regulates Remyelination via Glutamate Signalling to Oligodendrocyte Progenitors Nat. Commun. 2015 6 8518 10.1038/ncomms9518 26439639 PMC4600759 · DOI
  154. [162]Morioka N. Fujii S. Kondo S. Zhang F.F. Miyauchi K. Nakamura Y. Hisaoka-Nakashima K. Nakata Y. Downregulation of Spinal Astrocytic Connexin43 Leads to Upregulation of Interleukin-6 and Cyclooxygenase-2 and Mechanical Hypersensitivity in Mice Glia 2018 66 428 444 10.1002/glia.23255 29105869 · DOI
  155. [163]De Bock M. Kerrebrouck M. Wang N. Leybaert L. Neurological Manifestations of Oculodentodigital Dysplasia: A Cx43 Channelopathy of the Central Nervous System? Front. Pharmacol. 2013 4 120 10.3389/fphar.2013.00120 24133447 PMC3783840 · DOI
  156. [164]Jarvis S.E. Lee J.E. Jewlal E. Barr K. Kelly G.M. Laird D.W. Willmore K.E. Effects of Reduced Connexin43 Function on Skull Development in the Cx43I130T/+ Mutant Mouse That Models Oculodentodigital Dysplasia Bone 2020 136 115365 10.1016/j.bone.2020.115365 32320893 · DOI
  157. [165]Sargiannidou I. Christophidou-Anastasiadou V. Hadjisavvas A. Tanteles G.A. Kleopa K.A. Novel GJA1/Cx43 Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms Front. Genet. 2021 11 604806 10.3389/fgene.2020.604806 33584802 PMC7873484 · DOI
  158. [166]Esseltine J.L. Shao Q. Brooks C. Sampson J. Betts D.H. Séguin C.A. Laird D.W. Connexin43 Mutant Patient-Derived Induced Pluripotent Stem Cells Exhibit Altered Differentiation Potential: Altered Differentiation Potential in ODDD Patient IPSCS J. Bone Miner. Res. 2017 32 1368 1385 10.1002/jbmr.3098 28177159 · DOI
  159. [167]Hamida C.B. Cavalier L. Belal S. Sanhaji H. Nadal N. Barhoumi C. M’Rissa N. Marzouki N. Mandel J.-L. Hamida M.B. Homozygosity Mapping of Giant Axonal Neuropathy Gene to Chromosome 16q24.1 Neurogenetics 1997 1 129 133 10.1007/s100480050019 10732815 · DOI
  160. [168]Johnson-Kerner B.L. Ahmad F.S. Diaz A.G. Greene J.P. Gray S.J. Samulski R.J. Chung W.K. Van Coster R. Maertens P. Noggle S.A. Intermediate Filament Protein Accumulation in Motor Neurons Derived from Giant Axonal Neuropathy IPSCs Rescued by Restoration of Gigaxonin Hum. Mol. Genet. 2015 24 1420 1431 10.1093/hmg/ddu556 25398950 PMC4402342 · DOI
  161. [169]Lin N.-H. Huang Y.-S. Opal P. Goldman R.D. Messing A. Perng M.-D. The Role of Gigaxonin in the Degradation of the Glial-Specific Intermediate Filament Protein GFAP MBoC 2016 27 3980 3990 10.1091/mbc.E16-06-0362 27798231 PMC5156539 · DOI
  162. [170]Juopperi T.A. Kim W.R. Chiang C.-H. Yu H. Margolis R.L. Ross C.A. Ming G. Song H. Astrocytes Generated from Patient Induced Pluripotent Stem Cells Recapitulate Features of Huntington’s Disease Patient Cells Mol. Brain 2012 5 17 10.1186/1756-6606-5-17 22613578 PMC3506453 · DOI
  163. [171]Shaltouki A. Peng J. Liu Q. Rao M.S. Zeng X. Efficient Generation of Astrocytes from Human Pluripotent Stem Cells in Defined Conditions Stem Cells 2013 31 941 952 10.1002/stem.1334 23341249 · DOI
  164. [172]Lundin A. Delsing L. Clausen M. Ricchiuto P. Sanchez J. Sabirsh A. Ding M. Synnergren J. Zetterberg H. Brolén G. Human IPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models Stem Cell Rep. 2018 10 1030 1045 10.1016/j.stemcr.2018.01.021 PMC5918339 29456185 · DOI
  165. [173]Kang P. Lee H.K. Glasgow S.M. Finley M. Donti T. Gaber Z.B. Graham B.H. Foster A.E. Novitch B.G. Gronostajski R.M. Sox9 and NFIA Coordinate a Transcriptional Regulatory Cascade during the Initiation of Gliogenesis Neuron 2012 74 79 94 10.1016/j.neuron.2012.01.024 22500632 PMC3543821 · DOI · Paper page
  166. [174]Li X. Tao Y. Bradley R. Du Z. Tao Y. Kong L. Dong Y. Jones J. Yan Y. Harder C.R.K. Fast generation of functional subtype astrocytes from human pluripotent stem cells Stem Cell Rep. 2018 11 998 1008 10.1016/j.stemcr.2018.08.019 PMC6178885 30269954 · DOI
  167. [175]Neyrinck K. Van Den Daele J. Vervliet T. De Smedt J. Wierda K. Nijs M. Vanbokhoven T. D’hondt A. Planque M. Fendt S.-M. SOX9-Induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-Human System Stem Cell Rev. Rep. 2021 17 1855 1873 10.1007/s12015-021-10179-x 33982246 PMC8553725 · DOI
  168. [177]Holmqvist S. Brouwer M. Djelloul M. Diaz A.G. Devine M.J. Hammarberg A. Fog K. Kunath T. Roybon L. Generation of Human Pluripotent Stem Cell Reporter Lines for the Isolation of and Reporting on Astrocytes Generated from Ventral Midbrain and Ventral Spinal Cord Neural Progenitors Stem Cell Res. 2015 15 203 220 10.1016/j.scr.2015.05.014 26100233 · DOI
  169. [178]Zhang P.-W. Haidet-Phillips A.M. Pham J.T. Lee Y. Huo Y. Tienari P.J. Maragakis N.J. Sattler R. Rothstein J.D. Generation of GFAP::GFP Astrocyte Reporter Lines from Human Adult Fibroblast-Derived IPS Cells Using Zinc-Finger Nuclease Technology Glia 2016 64 63 75 10.1002/glia.22903 26295203 PMC4715664 · DOI
  170. [179]Mollinari C. Merlo D. Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach Neurochem. Res. 2021 46 1330 1336 10.1007/s11064-021-03282-5 33666839 PMC8084785 · DOI
  171. [180]Caiazzo M. Giannelli S. Valente P. Lignani G. Carissimo A. Sessa A. Colasante G. Bartolomeo R. Massimino L. Ferroni S. Direct Conversion of Fibroblasts into Functional Astrocytes by Defined Transcription Factors Stem Cell Rep. 2015 4 25 36 10.1016/j.stemcr.2014.12.002 PMC4297873 25556566 · DOI
  172. [181]Qiu B. de Vries R.J. Caiazzo M. Direct Cell Reprogramming of Mouse Fibroblasts into Functional Astrocytes Using Lentiviral Overexpression of the Transcription Factors NFIA, NFIB, and SOX9 Neural Reprogramming Ahlenius H. Methods in Molecular Biology Springer New York, NY, USA 2021 Volume 2352 31 43 978-1-07-161600-0 34324178
  173. [182]Masserdotti G. Gascón S. Götz M. Direct Neuronal Reprogramming: Learning from and for Development Development 2016 143 2494 2510 10.1242/dev.092163 27436039 · DOI
  174. [183]Liu C. Oikonomopoulos A. Sayed N. Wu J.C. Modeling Human Diseases with Induced Pluripotent Stem Cells: From 2D to 3D and Beyond Development 2018 145 dev156166 10.1242/dev.156166 29519889 PMC5868991 · DOI
  175. [184]Lancaster M.A. Knoblich J.A. Organogenesis in a Dish: Modeling Development and Disease Using Organoid Technologies Science 2014 345 1247125 10.1126/science.1247125 25035496 · DOI · Paper page
  176. [185]Mofazzal Jahromi M.A. Abdoli A. Rahmanian M. Bardania H. Bayandori M. Moosavi Basri S.M. Kalbasi A. Aref A.R. Karimi M. Hamblin M.R. Microfluidic Brain-on-a-Chip: Perspectives for Mimicking Neural System Disorders Mol. Neurobiol. 2019 56 8489 8512 10.1007/s12035-019-01653-2 31264092 PMC6842047 · DOI
  177. [186]Lancaster M.A. Renner M. Martin C.-A. Wenzel D. Bicknell L.S. Hurles M.E. Homfray T. Penninger J.M. Jackson A.P. Knoblich J.A. Cerebral Organoids Model Human Brain Development and Microcephaly Nature 2013 501 373 379 10.1038/nature12517 23995685 PMC3817409 · DOI · Paper page
  178. [189]Krencik R. Seo K. van Asperen J.V. Basu N. Cvetkovic C. Barlas S. Chen R. Ludwig C. Wang C. Ward M.E. Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes Stem Cell Rep. 2017 9 1745 1753 10.1016/j.stemcr.2017.10.026 29198827 PMC5785708 · DOI
  179. [191]Madhavan M. Nevin Z.S. Shick H.E. Garrison E. Clarkson-Paredes C. Karl M. Clayton B.L.L. Factor D.C. Allan K.C. Barbar L. Induction of Myelinating Oligodendrocytes in Human Cortical Spheroids Nat. Methods 2018 15 700 706 10.1038/s41592-018-0081-4 30046099 PMC6508550 · DOI · Paper page
  180. [192]Kim H. Park H.J. Choi H. Chang Y. Park H. Shin J. Kim J. Lengner C.J. Lee Y.K. Kim J. Modeling G2019S-LRRK2 Sporadic Parkinson’s Disease in 3D Midbrain Organoids Stem Cell Rep. 2019 12 518 531 10.1016/j.stemcr.2019.01.020 PMC6410341 30799274 · DOI
  181. [193]Shaker M.R. Pietrogrande G. Martin S. Lee J.-H. Sun W. Wolvetang E.J. Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids Front. Cell. Neurosci. 2021 15 631548 10.3389/fncel.2021.631548 33815061 PMC8010307 · DOI
  182. [194]James O.G. Selvaraj B.T. Magnani D. Burr K. Connick P. Barton S.K. Vasistha N.A. Hampton D.W. Story D. Smigiel R. IPSC-Derived Myelinoids to Study Myelin Biology of Humans Dev. Cell 2021 56 1346 1358.e6 10.1016/j.devcel.2021.04.006 33945785 PMC8098746 · DOI
  183. [195]Qi D. Wu S. Lin H. Kuss M.A. Lei Y. Krasnoslobodtsev A. Ahmed S. Zhang C. Kim H.J. Jiang P. Establishment of a Human IPSC- and Nanofiber-Based Microphysiological Blood–Brain Barrier System ACS Appl. Mater. Interfaces 2018 10 21825 21835 10.1021/acsami.8b03962 29897225 PMC6052796 · DOI · Paper page
  184. [196]Huang K. Castiaux A.D. Podicheti R. Rusch D.B. Martin R.S. Baker L.A. A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model Small Methods 2021 5 2100592 10.1002/smtd.202100592 34541301 PMC8445000 · DOI
  185. [197]Lippmann E.S. Azarin S.M. Kay J.E. Nessler R.A. Wilson H.K. Al-Ahmad A. Palecek S.P. Shusta E.V. Derivation of Blood-Brain Barrier Endothelial Cells from Human Pluripotent Stem Cells Nat. Biotechnol. 2012 30 783 791 10.1038/nbt.2247 22729031 PMC3467331 · DOI · Paper page
  186. [198]Bhalerao A. Sivandzade F. Archie S.R. Chowdhury E.A. Noorani B. Cucullo L. In Vitro Modeling of the Neurovascular Unit: Advances in the Field Fluids Barriers CNS 2020 17 22 10.1186/s12987-020-00183-7 32178700 PMC7077137 · DOI
  187. [199]Delsing L. Herland A. Falk A. Hicks R. Synnergren J. Zetterberg H. Models of the Blood-Brain Barrier Using IPSC-Derived Cells Mol. Cell. Neurosci. 2020 107 103533 10.1016/j.mcn.2020.103533 32717317 · DOI
  188. [200]Staicu C.E. Jipa F. Axente E. Radu M. Radu B.M. Sima F. Lab-on-a-Chip Platforms as Tools for Drug Screening in Neuropathologies Associated with Blood–Brain Barrier Alterations Biomolecules 2021 11 916 10.3390/biom11060916 34205550 PMC8235582 · DOI
  189. [202]Potjewyd G. Kellett K.A.B. Hooper N.M. 3D Hydrogel Models of the Neurovascular Unit to Investigate Blood–Brain Barrier Dysfunction Neuronal Signal. 2021 5 NS20210027 10.1042/NS20210027 34804595 PMC8579151 · DOI
  190. [203]Mertens J. Reid D. Lau S. Kim Y. Gage F.H. Aging in a Dish: IPSC-Derived and Directly Induced Neurons for Studying Brain Aging and Age-Related Neurodegenerative Diseases Annu. Rev. Genet. 2018 52 271 293 10.1146/annurev-genet-120417-031534 30208291 PMC6415910 · DOI
  191. [204]Gascón S. Masserdotti G. Russo G.L. Götz M. Direct Neuronal Reprogramming: Achievements, Hurdles, and New Roads to Success Cell Stem Cell 2017 21 18 34 10.1016/j.stem.2017.06.011 28686866 · DOI
  192. [205]Marton R.M. Pașca S.P. Organoid and Assembloid Technologies for Investigating Cellular Crosstalk in Human Brain Development and Disease Trends Cell Biol. 2020 30 133 143 10.1016/j.tcb.2019.11.004 31879153 · DOI

Authors
Lanciotti, A., Brignone, M. S., Macioce, P., Visentin, S., & Ambrosini, E.
Affiliations
Istituto Superiore di Sanità (IT)
Corresponding author
Ambrosini, Elena
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-12-27
Volume
23
Issue
1
Pages
274
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms23010274
PMC
PMC8745131
OpenAlex
W4200276827
Cited by
14
References
205
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3
FWCI
0.21
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministero della Salute ("5 x 1000"., GR-2013-02355882)
  • Istituto Superiore di Sanità (ISS5x1000_21-949432e8c9be)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
astrocytes, leukodystrophy, induced pluripotent stem cells, astrocyte dysfunction, myelin, demyelinating disease, disease modeling, white matter pathology, astrocyte differentiation
MeSH terms
Astrocytes, Cell Differentiation, Humans, Models, Biological, Myelin Sheath, Leukoencephalopathies, Induced Pluripotent Stem Cells

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