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Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells.

Neuron | 2017

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.

Pubmed ID: 28817799 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS081703
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007365
  • Agency: NIMH NIH HHS, United States
    Id: F30 MH106261
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH107800
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001085
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH099555

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