Tweaking neural organoids to model human reactive astrocytes

Abstract

The study of human reactive astrocytes has been limited by resource availability. In this issue, Cvetkovic et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202107135) develop multicellular organoid systems containing mature astrocytes to study the dynamics of human astrocytes reactivity and its downstream effects on neuronal activity.

Figure 1.

Human brain organoid system developed by Cvetkovic et al. Human induced pluripotent stem cells (hiPSCs) are differentiated into chemogenetic astrocytes (i.e., Astrostim) expressing modified human M3 muscarinic Gq protein-coupled (hM3Dq) receptors and into optogenetic neurons (i.e., Optoneurons) harboring Channelrhodopsin 2 (ChR2). The generation of multi-cellular sphere co-cultures of Optoneurons and Astrostims allows for dual specific modulation of calcium responses in astrocytes upon application of clozapine-N-oxidase (CNO) and for an increase in neuronal activity upon light stimulation.