title: Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Joon-Ik
authors.initials: JI
authors.lastname: Ahn
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Lee
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Shim
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Lee
authors.forename: Sung Yeoul
authors.initials: SY
authors.lastname: Chang
authors.forename: Young-Seek
authors.initials: YS
authors.lastname: Lee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brownstein
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Lee
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA