Comparison of the gene expression profiles of human fetal cortical astrocytes with pluripotent stem cell derived neural stem cells identifies human astrocyte markers and signaling pathways and transcription factors active in human astrocytes

PLoS One. 2014 May 21;9(5):e96139. doi: 10.1371/journal.pone.0096139. eCollection 2014.

Abstract

Astrocytes are the most abundant cell type in the central nervous system (CNS) and have a multitude of functions that include maintenance of CNS homeostasis, trophic support of neurons, detoxification, and immune surveillance. It has only recently been appreciated that astrocyte dysfunction is a primary cause of many neurological disorders. Despite their importance in disease very little is known about global gene expression for human astrocytes. We have performed a microarray expression analysis of human fetal astrocytes to identify genes and signaling pathways that are important for astrocyte development and maintenance. Our analysis confirmed that the fetal astrocytes express high levels of the core astrocyte marker GFAP and the transcription factors from the NFI family which have been shown to play important roles in astrocyte development. A group of novel markers were identified that distinguish fetal astrocytes from pluripotent stem cell-derived neural stem cells (NSCs) and NSC-derived neurons. As in murine astrocytes, the Notch signaling pathway appears to be particularly important for cell fate decisions between the astrocyte and neuronal lineages in human astrocytes. These findings unveil the repertoire of genes expressed in human astrocytes and serve as a basis for further studies to better understand astrocyte biology, especially as it relates to disease.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Astrocytes / metabolism*
  • Biomarkers / metabolism
  • Cell Dedifferentiation
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Fetus / cytology
  • Gene Ontology
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptome*
  • Up-Regulation

Substances

  • Biomarkers
  • Transcription Factors

Grants and funding

This research was supported by the National Institutes of Health (NIH) Common Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.