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.
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.
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America.
Nasir
N
Malik
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America.
Xiantao
X
Wang
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America.
Sonia
S
Shah
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America.
Anastasia G
AG
Efthymiou
Hong Kong Baptist University, Department of Biology, Hong Kong.
Bin
B
Yan
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America.
Sabrina
S
Heman-Ackah
The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, United States of America.
Ming
M
Zhan
National Institutes of Health, NIAMS, Bethesda, Maryland, United States of America; National Institutes of Health, NIH Center for Regenerative Medicine, Bethesda, Maryland, United States of America.
Mahendra
M
Rao
D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D054337:Cell Dedifferentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005333:Fetus / Q000166:cytology; D063990:Gene Ontology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
D015415:Biomarkers; D014157:Transcription Factors