CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes.

Autor:	Barbar L; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Jain T; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Zimmer M; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Kruglikov I; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Sadick JS; Neuroscience Institute, NYU Langone School of Medicine, New York, NY 10016, USA., Wang M; Department of Genetics & Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Kalpana K; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Rose IVL; Neuroscience Institute, NYU Langone School of Medicine, New York, NY 10016, USA., Burstein SR; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Rusielewicz T; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Nijsure M; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Guttenplan KA; Department of Neurobiology, Stanford University, Stanford, CA 94305, USA., di Domenico A; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Croft G; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA., Zhang B; Department of Genetics & Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Nobuta H; Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Hébert JM; Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Liddelow SA; Neuroscience Institute, NYU Langone School of Medicine, New York, NY 10016, USA; Department of Neuroscience and Physiology, NYU Langone School of Medicine, New York, NY 10016, USA; Department of Ophthalmology, NYU Langone School of Medicine, New York, NY 10017, USA., Fossati V; The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA. Electronic address: vfossati@nyscf.org.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2020 Aug 05; Vol. 107 (3), pp. 436-453.e12. Date of Electronic Publication: 2020 Jun 01.
DOI:	10.1016/j.neuron.2020.05.014
Abstrakt:	New methods for investigating human astrocytes are urgently needed, given their critical role in the central nervous system. Here we show that CD49f is a novel marker for human astrocytes, expressed in fetal and adult brains from healthy and diseased individuals. CD49f can be used to purify fetal astrocytes and human induced pluripotent stem cell (hiPSC)-derived astrocytes. We provide single-cell and bulk transcriptome analyses of CD49f + hiPSC-astrocytes and demonstrate that they perform key astrocytic functions in vitro, including trophic support of neurons, glutamate uptake, and phagocytosis. Notably, CD49f + hiPSC-astrocytes respond to inflammatory stimuli, acquiring an A1-like reactive state, in which they display impaired phagocytosis and glutamate uptake and fail to support neuronal maturation. Most importantly, we show that conditioned medium from human reactive A1-like astrocytes is toxic to human and rodent neurons. CD49f + hiPSC-astrocytes are thus a valuable resource for investigating human astrocyte function and dysfunction in health and disease. Competing Interests: Declaration of Interests S.A.L. is an academic founder of AstronauTx Ltd. NYSCF. U.S. patent pending. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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