1. CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes
- Author
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Jessica S. Sadick, Suzanne R. Burstein, Kriti Kalpana, Valentina Fossati, I. A. Kruglikov, Hiroko Nobuta, Indigo V.L. Rose, Angelique di Domenico, Kevin A. Guttenplan, Tomasz Rusielewicz, Matthew Zimmer, Gist F. Croft, Shane A. Liddelow, Minghui Wang, Tanya Jain, Lilianne Barbar, Madhura P. Nijsure, Bin Zhang, and Jean M. Hébert
- Subjects
0301 basic medicine ,Patch-Clamp Techniques ,Phagocytosis ,Induced Pluripotent Stem Cells ,Central nervous system ,Glutamic Acid ,Integrin alpha6 ,Biology ,Article ,Transcriptome ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Single-cell analysis ,Alzheimer Disease ,medicine ,Animals ,Humans ,RNA-Seq ,Induced pluripotent stem cell ,Inflammation ,Gene Expression Profiling ,General Neuroscience ,Neurodegeneration ,Neurotoxicity ,Flow Cytometry ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Astrocytes ,Single-Cell Analysis ,Biomarkers ,030217 neurology & neurosurgery ,Astrocyte - Abstract
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.
- Published
- 2020
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