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

• Published in: PloS one 2014-05, Vol.9 (5), p.e96139-e96139
• Main Authors: Malik, Nasir, Wang, Xiantao, Shah, Sonia, Efthymiou, Anastasia G, Yan, Bin, Heman-Ackah, Sabrina, Zhan, Ming, Rao, Mahendra
• Format: Article
• Language: English
• Subjects: Astrocytes; Astrocytes - metabolism; Biology; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Cell culture; Cell Dedifferentiation; Cell fate; Cells, Cultured; Central nervous system; Cerebral Cortex - cytology; Comparative analysis; Cortex; Detoxification; DNA binding proteins; DNA microarrays; Epidermal growth factor; Fetus - cytology; Fetuses; Gene expression; Gene Ontology; Genes; Glial fibrillary acidic protein; Homeostasis; Human performance; Humans; Immunosurveillance; Induced Pluripotent Stem Cells - metabolism; Intermediate filament proteins; Nervous system; Nervous system diseases; Neural stem cells; Neural Stem Cells - physiology; Neurological diseases; Neurons; Notch protein; Nuclear factor I; Oligonucleotide Array Sequence Analysis; Phase transitions; Pluripotency; Proteins; Rodents; Signal Transduction; Signaling; Stem cell transplantation; Stem cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptome; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096139

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.