1. Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells.
- Author
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Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, Reimer R, Quake SR, Barres BA, and Paşca SP
- Subjects
- Cell Differentiation physiology, Cells, Cultured, Fetus, Humans, Imaging, Three-Dimensional, Transcription Factors genetics, Transcription Factors metabolism, Astrocytes physiology, Cerebral Cortex cytology, Models, Biological, Pluripotent Stem Cells physiology
- Abstract
There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells. We found that hCS-derived glia closely resemble primary human fetal astrocytes and that, over time in vitro, they transition from a predominantly fetal to an increasingly mature astrocyte state. Transcriptional changes in astrocytes are accompanied by alterations in phagocytic capacity and effects on neuronal calcium signaling. These findings suggest that hCS-derived astrocytes closely resemble primary human astrocytes and can be used for studying development and modeling disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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