An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

Stem Cell Reports. 2017 Aug 8;9(2):600-614. doi: 10.1016/j.stemcr.2017.06.018. Epub 2017 Jul 27.

Abstract

Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

Keywords: astrocyte; human induced pluripotent stem cell; iPSC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Calcium / metabolism
  • Cell Culture Techniques
  • Cell Differentiation* / genetics
  • Cells, Cultured
  • Computational Biology / methods
  • Cytokines / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Microglia / immunology
  • Microglia / metabolism
  • Molecular Sequence Annotation
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Phagocytosis
  • Transcriptome

Substances

  • Cytokines
  • Calcium