Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties

Development. 2019 Jul 8;146(13):dev170910. doi: 10.1242/dev.170910.

Abstract

Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially in humans, is unknown. RNA-seq of human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential functional properties. This was confirmed by differential calcium signaling as well as effects on neurite growth and blood-brain barrier formation. Distinct transcriptional profiles and functional properties of human astrocytes generated from regionally specified neural progenitors under the same conditions strongly implicate the developmental impact on astrocyte diversity. These findings provide a rationale for renewed examination of regional astrocytes and their role in the pathogenesis of psychiatric and neurological disorders.

Keywords: Astrocyte heterogeneity; Blood-brain barrier; Human astrocyte development; Neuron-glia interaction; RNA-seq.

Publication types

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

MeSH terms

  • Astrocytes / physiology*
  • Base Sequence
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Neural Stem Cells / physiology
  • Neurogenesis / genetics*
  • Organ Specificity / genetics
  • Pluripotent Stem Cells / physiology*
  • Prosencephalon / cytology
  • Prosencephalon / metabolism
  • Sequence Analysis, RNA
  • Transcriptome*

Substances

  • Biomarkers