Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons.
Neurogenesis is one of the most complex events in embryonic development. However, little information is available regarding the molecular events that occur during neurogenesis. To identify regulatory genes and underlying mechanisms involved in the differentiation of embryonic stem (ES) cells to neurons, gene expression profiling was performed using cDNA microarrays. In mouse ES cells, we compared the gene expression of each differentiated cell stage using a five-stage lineage selection method. Of 10,368 genes, 1633 (16%) known regulatory genes were differentially expressed at least 2-fold or greater at one or more stages. At stage 3, during which ES cells differentiate into neural stem cells, modulation of nearly 1000 genes was observed. Most of transcription factors (Otx2, Ebf-3, Ptx3, Sox4, 13, 18, engrailed, Irx2, Pax8, and Lim3), signaling molecules (Wnt, TGF, and Shh family members), and extracellular matrix/adhesion molecules (collagens, MAPs, and NCAM) were up-regulated. However, some genes which may play important roles in maintaining the pluripotency of ES cells (Kruppel-like factor 2, 4, 5, 9, myeloblast oncogene like2, ZFP 57, and Esg-1) were down-regulated. The many genes identified with this approach that are modulated during neurogenesis will facilitate studies of the mechanisms underlying ES cell differentiation, neural induction, and neurogenesis.
Ahn
Joon-Ik
JI
Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
Lee
Ki-Hwan
KH
Shin
Dong-Mi
DM
Shim
Jae-Won
JW
Lee
Jae-Seong
JS
Chang
Sung Yeoul
SY
Lee
Young-Seek
YS
Brownstein
Michael J
MJ
Lee
Sang-Hun
SH
Lee
Yong-Sung
YS
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020869:Gene Expression Profiling; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012249:Rhombencephalon / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA