Stem cell-derived brainstem mouse astrocytes obtain a neurotoxic phenotype in vitro upon neuroinflammation

Freeman MR. Specification and morphogenesis of astrocytes. Science (1979). 2010/11/06. Department of Neurobiology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. marc.freeman@umassmed.edu; 2010;330:774–8.

Moulson AJ, Squair JW, Franklin RJM, Tetzlaff W, Assinck P. Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? Front Cell Neurosci. 2021;15.

Anderson MA, Ao Y, Sofroniew M V. Heterogeneity of reactive astrocytes. Neurosci Lett. 2013/12/24. Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095–1763, United States. Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, C; 2014;565:23–9.

Sofroniew MV. Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity. Trends Immunol The Author. 2020;41:758–70.

Article  CAS  Google Scholar 

Escartin C, Galea E, Lakatos A, O’Callaghan JP, Petzold GC, Serrano-Pozo A, et al. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci. 2021;24:312–25 Springer US.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. J Neurosci. 2012/05/04. Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305–5125, USA. jlz@stanford.edu; 2012;32:6391–410.

Sofroniew MV. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci Nature Publishing Group. 2015;16:249–63.

Article  CAS  Google Scholar 

Anderson MA, Ao Y, Sofroniew MV. Heterogeneity of reactive astrocytes. Neurosci Lett Elsevier Ireland Ltd. 2014;565:23–9.

Article  CAS  Google Scholar 

Hasel P, Rose IVL, Sadick JS, Kim RD, Liddelow SA. Neuroinflammatory astrocyte subtypes in the mouse brain. Nat Neurosci. 2021;24:1475–87.

Article  CAS  PubMed  Google Scholar 

Abu Hamdeh S, Marklund N, Lannsjö M, Howells T, Raininko R, Wikström J, et al. Extended Anatomical Grading in Diffuse Axonal Injury Using MRI: Hemorrhagic Lesions in the Substantia Nigra and Mesencephalic Tegmentum Indicate Poor Long-Term Outcome. J Neurotrauma. 2017;34:341–52.

Article  PubMed  PubMed Central  Google Scholar 

Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, Mclellan DR. Diffuse axonal injury in head injury: Definition, diagnosis and grading. Histopathology. 1989;15:49–59.

Article  CAS  PubMed  Google Scholar 

Stahel PF, Kossmann T, Morganti-Kossmann MC, Hans VHJ, Barnum SR. Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Mole Brain Res Elsevier. 1997;50:205–12.

Article  CAS  Google Scholar 

Hans VHJ, Kossmann T, Lenzlinger PM, Probstmeier R, Imhof HG, Trentz O, et al. Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid. J Cereb Blood Flow Metab. 1999;19:184–94.

Article  CAS  PubMed  Google Scholar 

Medana IM, Esiri MM. Axonal damage: A key predictor of outcome in human CNS diseases. Brain. 2003;126:515–30.

Article  CAS  PubMed  Google Scholar 

Ekmark-Lewén S, Flygt J, Kiwanuka O, Meyerson BJ, Lewén A, Hillered L, et al. Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes. J Neuroinflammation. 2013;10:1–19.

Article  Google Scholar 

Csuka E, Hans VHJ, Ammann E, Trentz O, Kossmann T, Morganti-Kossmann MC. Cell activation and inflammatory response following traumatic axonal injury in the rat. NeuroReport. 2000;11:2587–90.

Article  CAS  PubMed  Google Scholar 

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541:481–7. https://doi.org/10.1038/nature21029. Nature Publishing Group.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clarke BE, Taha DM, Ziff OJ, Alam A, Thelin EP, Garcia NM, et al. Human stem cell-derived astrocytes exhibit region-specific heterogeneity in their secretory profiles. Brain. 2020;143:8–11.

Article  Google Scholar 

Barbar L, Jain T, Zimmer M, Kruglikov I, Sadick JS, Wang M, et al. CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes. Neuron. 2020;107:436-453.e12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci. 2007;10:615–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Statens jordbruksverks författningssamling [Internet]. 2019 [cited 2020 Mar 13]. Available from: http://www.jordbruksverket.se/download/18.7c1e1fce169bee5214fad877/1553851490782/2019-009.pdf

Wichterle H, Lieberam I, Porter JA, Jessell TM. Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002/08/15. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.; 2002;110:385–97.

Kleiderman S, Sá JV, Teixeira AP, Brito C, Gutbier S, Evje LG, et al. Functional and phenotypic differences of pure populations of stem cell-derived astrocytes and neuronal precursor cells. Glia. 2016;64:695–715.

Article  PubMed  Google Scholar 

Roybon L, Lamas NJ, Garcia-Diaz A, Yang EJ, Sattler R, Jackson-Lewis V, et al. Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes. Cell Rep The Authors. 2013;4:1035–48.

Article  CAS  Google Scholar 

Kim BJ, Kim SS, Kim YI, Paek SH, Lee YD, Suh-Kim H. Forskolin promotes astroglial differentiation of human central neurocytoma cells. Exp Mol Med. 2004;36:52–6.

Article  CAS  PubMed  Google Scholar 

McManus MF, Chen LC, Vallejo I, Vallejo M. Astroglial differentiation of cortical precursor cells triggered by activation of the cAMP-dependent signaling pathway. J Neurosci. 1999/10/12. Reproductive Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.; 1999;19:9004–15.

Rajan P, McKay RDG. Multiple routes to astrocytic differentiation in the CNS. J Neurosci. 1998;18:3620–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, et al. Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science (1979). 1997/10/23. Division of Neuroscience, Children’s Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.; 1997;278:477–83.

Kitchen P, Salman MM, Halsey AM, Clarke-Bland C, MacDonald JA, Ishida H, et al. Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema. Cell. 2020;181:784-799.e19.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell Cell Press. 1999;96:25–34.

CAS  Google Scholar 

Covacu R, Danilov AI, Rasmussen BS, Hallén K, Moe MC, Lobell A, et al. Nitric Oxide Exposure Diverts Neural Stem Cell Fate from Neurogenesis Towards Astrogliogenesis. Stem Cells Wiley. 2006;24:2792–800.

Article  CAS  Google Scholar 

Burda JE, Bernstein AM, Sofroniew M V. Astrocyte roles in traumatic brain injury. Exp Neurol. Elsevier Inc.; 2016;275:305–15.

Lindblad C, Pin E, Just D, Al Nimer F, Nilsson P, Bellander B-M, et al. Fluid Proteomics of CSF and Serum Reveal Important Neuroinammatory Proteins in Blood-Brain Barrier Disruption and Outcome Prediction Following Severe Traumatic Brain Injury: A Prospective, Observational Study. Crit Care [Internet]. BioMed Central; 2021;1–28. Available from: https://doi.org/10.21203/rs.3.rs-96625/v1

Okusawa BYS, W KIMBYJOS, Meer MVANDER, Endres S, Lonnemann G, Hefter K, et al. C5a STIMULATES SECRETION OF TUMOR NECROSIS Comparison with Secretion of Interleukin 10 and Interleukin la. 1988;168.

Webster RO, Hong SR, Johnston RB, Henson PM. Biological Effects of the Human Complement Fragments C5a and C5ades Arg on Neutrophil Function. 1980;219:201–19.

Thelin EP, Hall CE, Gupta K, Carpenter KLH, Chandran S, Hutchinson PJ, et al. Elucidating Pro-Inflammatory Cytokine Responses after Traumatic Brain Injury in a Human Stem Cell Model. J Neurotrauma. 2018;35:341–52.

Article  PubMed  PubMed Central  Google Scholar 

Thelin EP, Hall CE, Tyzack GE, Frostell A, Giorgi-Coll S, Alam A, et al. Delineating Astrocytic Cytokine Responses in a Human Stem Cell Model of Neural Trauma. J Neurotrauma. 2020;37:93–105.

Article  PubMed  Google Scholar 

Skiljan I. IrfanView - Official Homepage - One of the Most Popular Viewers Worldwide [Internet]. [cited 2021 Nov 22]. Available from: https://www.irfanview.com/

Berglund R, Guerreiro-Cacais AO, Adzemovic MZ, Zeitelhofer M, Lund H, Ewing E, et al. Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation. Sci Immunol. 2020;5.

Hedlund E, Pruszak J, Lardaro T, Ludwig W, Viñuela A, Kim K-S, et al. Embryonic Stem Cell-Derived Pitx3-Enhanced Green Fluorescent Protein Midbrain Dopamine Neurons Survive Enrichment by Fluorescence-Activated Cell Sorting and Function in an Animal Model of Parkinson’s Disease. Stem Cells. 2008;26:1526–36.

Article  CAS  PubMed  Google Scholar 

Allodi I, Nijssen J, Benitez JA, Schweingruber C, Fuchs A, Bonvicini G, et al. Modeling Motor Neuron Resilience in ALS Using Stem Cells. Stem Cell Reports ElsevierCompany. 2019;12:1329–41.

Article  CAS  Google Scholar 

Zachariadis V, Cheng H, Andrews N, Enge M. A Highly Scalable Method for Joint Whole-Genome Sequencing and Gene-Expression Profiling of Single Cells. Mol Cell.  2020;80:541–553.e5. Elsevier Inc.

Zachariadis V, Cheng H, Andrews N, Enge M. Direct nuclear tagmentation and RNA-sequencing ( DNTR- seq ). protocols.io. 2020;

Zhu YY, Machleder EM, Chenchik A, Li R, Siebert PD. Reverse transcriptase template switching: A SMART™ approach for full-length cDNA library construction. Biotechniques. 2001;30:892–7.

Article  CAS  PubMed  Google Scholar 

Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, et al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat Biotechnol. 2012;30:777–82.

Article  PubMed  PubMed Central  Google Scholar 

Picelli S, Faridani OR, Björklund ÅK, Winberg G, Sagasser S, Sandberg R. Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc. 2014;9:171–81.

Article  CAS  PubMed  Google Scholar 

Adey A, Morrison HG, Asan, Xun X, Kitzman JO, Turner EH, et al. Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition. Genome Biol. 2010;11.

Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.

Article  CAS  PubMed  Google Scholar 

Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30:207–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Team RC. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018.

Neuwirth E. RColorBrewer: ColorBrewer Palettes. 2014.

Wilke CO. cowplot: Streamlined Plot Theme and Plot Annotations for “ggplot2.” Comprehensive R Archive Network (CRAN); 2019.

Auguie B. gridExtra: Miscellaneous Functions for “Grid” Graphics. Comprehensive R Archive Network (CRAN); 2017.

Wickham H, Averick M, Bryan J,

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