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

Neuron. 2020 Aug 5;107(3):436-453.e12. doi: 10.1016/j.neuron.2020.05.014.

Lilianne Barbar ¹, Tanya Jain ¹, Matthew Zimmer ¹, Ilya Kruglikov ¹, Jessica S Sadick ², Minghui Wang ³, Kriti Kalpana ¹, Indigo V L Rose ², Suzanne R Burstein ¹, Tomasz Rusielewicz ¹, Madhura Nijsure ¹, Kevin A Guttenplan ⁴, Angelique di Domenico ¹, Gist Croft ¹, Bin Zhang ³, Hiroko Nobuta ⁵, Jean M Hébert ⁵, Shane A Liddelow ⁶, Valentina Fossati ⁷

Affiliations

1 The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
2 Neuroscience Institute, NYU Langone School of Medicine, New York, NY 10016, USA.
3 Department of Genetics & Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4 Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.
5 Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
6 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.
7 The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA. Electronic address: [email protected].

PMID: 32485136 DOI: 10.1016/j.neuron.2020.05.014

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.

Keywords

A1 reactive astrocytes; CD49f; FACS purification; astrocytes; induced pluripotent stem cells; neurodegeneration; neurotoxicity.

Name
Email *

	Sorry, but the email address you supplied was invalid.