We have been developing tools and resources that make it possible to analyze a large number of genes in various experimental conditions. In our earlier work, we 1) constructed cDNA libraries from early mouse embryos and stem cells and generated a large number of expressed sequence tags (ESTs), 2) developed a glass-slide microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 44,000 unique mouse transcripts, 3) produced web-based ANOVA-FDR software to provide user-friendly microarray data analysis, and 4) developed an algorithm and a fully-automated computational pipeline for transcript assembly from expressed sequences aligned to the mouse genome. In addition, we recently developed a comprehensive database and web browser of the binding sites of transcription factors (TFs) and cis-regulatory modules (CRMs) on the mouse genome. These resources and tools are now applied to the systematic analysis of gene regulatory networks in mouse embryonic stem cells. In our pilot project, we have demonstrated that it is possible to analyze and identify downstream target genes by monitoring the global gene expression patterns of mouse ES cell lines, when a gene encoding a specific TF (Pou5f1 or Oct34 or Oct4 in this case) is manipulated so that the gene can be overexpressed or repressed. We are now extending this strategy to many transcription factors. In particular, during the last year, we have extended this strategy to other key transcription factors (Sox2 and Nanog) in mouse ES cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000656-10
Application #
7732273
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2008
Total Cost
$345,403
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sharov, Alexei A (2017) Composite Agency: Semiotics of Modularity and Guiding Interactions. Biosemiotics 10:157-178
Sharov, Alexei A (2016) Coenzyme world model of the origin of life. Biosystems 144:8-17
Sharov, Alexei A (2016) Evolutionary biosemiotics and multilevel construction networks. Biosemiotics 9:399-416
Teratani-Ota, Yusuke; Yamamizu, Kohei; Piao, Yulan et al. (2016) Induction of specific neuron types by overexpression of single transcription factors. In Vitro Cell Dev Biol Anim 52:961-973
Livigni, Alessandra; Peradziryi, Hanna; Sharov, Alexei A et al. (2013) A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. Curr Biol 23:2233-2244
Morgani, Sophie M; Canham, Maurice A; Nichols, Jennifer et al. (2013) Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep 3:1945-57
Hammachi, Fella; Morrison, Gillian M; Sharov, Alexei A et al. (2012) Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency. Cell Rep 1:99-109
Canham, Maurice A; Sharov, Alexei A; Ko, Minoru S H et al. (2010) Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript. PLoS Biol 8:e1000379
Kunisada, Makoto; Cui, Chang-Yi; Piao, Yulan et al. (2009) Requirement for Shh and Fox family genes at different stages in sweat gland development. Hum Mol Genet 18:1769-78
Sharova, Lioudmila V; Sharov, Alexei A; Nedorezov, Timur et al. (2009) Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res 16:45-58

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