TY - JOUR
T1 - Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks
AU - Karsten, Stanislav L.
AU - Kudo, Lili C.
AU - Jackson, Robert
AU - Sabatti, Chiara
AU - Kornblum, Harley I.
AU - Geschwind, Daniel H.
N1 - Funding Information:
We thank the UCLA microarray facility for providing the mouse 9K arrays and Jing Ou for preparation of the cultures. We received support from the NIMH: MH62800 and MH065756. S.L.K. is supported by the French Foundation for Alzheimer's Disease Research. We thank James Waschek for the Gli and SHH gene-specific primers for PCR.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - The genetic programs underlying neural stem cell (NSC) proliferation and pluripotentiality have only been partially elucidated. We compared the gene expression profile of proliferating neural stem cell cultures (NS) with cultures differentiated for 24 h (DC) to identify functionally coordinated alterations in gene expression associated with neural progenitor proliferation. The majority of differentially expressed genes (65%) were upregulated in NS relative to DC. Microarray analysis of this in vitro system was followed by high throughput screening in situ hybridization to identify genes enriched in the germinal neuroepithelium, so as to distinguish those expressed in neural progenitors from those expressed in more differentiated cells in vivo. NS cultures were characterized by the coordinate upregulation of genes involved in cell cycle progression, DNA synthesis, and metabolism, not simply related to general features of cell proliferation, since many of the genes identified were highly enriched in the CNS ventricular zones and not widely expressed in other proliferating tissues. Components of specific metabolic and signal transduction pathways, and several transcription factors, including Sox3, FoxM1, and PTTG1, were also enriched in neural progenitor cultures. We propose a putative network of gene expression linking cell cycle control to cell fate pathways, providing a framework for further investigations of neural stem cell proliferation and differentiation.
AB - The genetic programs underlying neural stem cell (NSC) proliferation and pluripotentiality have only been partially elucidated. We compared the gene expression profile of proliferating neural stem cell cultures (NS) with cultures differentiated for 24 h (DC) to identify functionally coordinated alterations in gene expression associated with neural progenitor proliferation. The majority of differentially expressed genes (65%) were upregulated in NS relative to DC. Microarray analysis of this in vitro system was followed by high throughput screening in situ hybridization to identify genes enriched in the germinal neuroepithelium, so as to distinguish those expressed in neural progenitors from those expressed in more differentiated cells in vivo. NS cultures were characterized by the coordinate upregulation of genes involved in cell cycle progression, DNA synthesis, and metabolism, not simply related to general features of cell proliferation, since many of the genes identified were highly enriched in the CNS ventricular zones and not widely expressed in other proliferating tissues. Components of specific metabolic and signal transduction pathways, and several transcription factors, including Sox3, FoxM1, and PTTG1, were also enriched in neural progenitor cultures. We propose a putative network of gene expression linking cell cycle control to cell fate pathways, providing a framework for further investigations of neural stem cell proliferation and differentiation.
KW - Cell fate
KW - Microarray analysis
KW - Neural stem cell
KW - Neurogenesis
KW - Regulatory network
UR - http://www.scopus.com/inward/record.url?scp=0041661947&partnerID=8YFLogxK
U2 - 10.1016/S0012-1606(03)00274-4
DO - 10.1016/S0012-1606(03)00274-4
M3 - Article
C2 - 12941627
AN - SCOPUS:0041661947
SN - 0012-1606
VL - 261
SP - 165
EP - 182
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -