Robust Induction of Functional Astrocytes Using NGN2 Expression in Human Pluripotent Stem Cells

Overview

Journal iScience

Publisher Cell Press

Date 2023 Aug 3

PMID 37534135

Authors

Martin H Berryer

Matthew Tegtmeyer

Loic Binan

Vera Valakh

Anna Nathanson

Darina Trendafilova

Ethan Crouse

Jenny A Klein

Daniel Meyer

Olli Pietilainen

Francesca Rapino

Samouil L Farhi

Lee L Rubin

Steven A McCarroll

Ralda Nehme

Lindy E Barrett

Affiliations

Soon will be listed here.

Abstract

Emerging evidence of species divergent features of astrocytes coupled with the relative inaccessibility of human brain tissue underscore the utility of human pluripotent stem cell (hPSC) technologies for the generation and study of human astrocytes. However, existing approaches for hPSC-astrocyte generation are typically lengthy or require intermediate purification steps. Here, we establish a rapid and highly scalable method for generating functional human induced astrocytes (hiAs). These hiAs express canonical astrocyte markers, respond to pro-inflammatory stimuli, exhibit ATP-induced calcium transients and support neuronal network development. Moreover, single-cell transcriptomic analyses reveal the generation of highly reproducible cell populations across individual donors, mostly resembling human fetal astrocytes. Finally, hiAs generated from a trisomy 21 disease model identify expected alterations in cell-cell adhesion and synaptic signaling, supporting their utility for disease modeling applications. Thus, hiAs provide a valuable and practical resource for the study of basic human astrocyte function and dysfunction in disease.

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