Abstract

The goal of this research project is to understand the nature of mouse embryonic and adult stem cells and to identify genes that are responsible for the maintenance of cellular pluripotency. We have been conducting global gene expression profiling with the mouse embryonic DNA microarrays developed in our laboratory. We have now completed the expression profiling of mouse embryonic stem (ES) cells, trophoblast stem (TS) cells, adult neural stem (NS) cells, ES cells undergoing neural differentiation in culture, F9 embryonal carcinoma (EC) cells undergoing endoderm differentiation, and ES cells undergoing trophoblast differentiation. We are currently analyzing these data by Principal Component Analysis (PCA) and other statistical and bioinformatic analyses. We have also completed the microarray analysis of ES cells, in which the level of Oct3/4 - a gene critical for maintenance of undifferentiated ES cells - is controlled by tetracycline-inducible system, and have identified a number of downstream target genes of Oct3/4. These studies begin to provide the gene regulatory pathways involved in the maintenance and differentiation of stem cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000662-05
Application #
7132307
Study Section
(LG)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
Sun, Chuanhai; Nakatake, Yuhki; Akagi, Tadayuki et al. (2009) Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. Mol Cell Biol 29:4574-83
Aiba, Kazuhiro; Nedorezov, Timur; Piao, Yulan et al. (2009) Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells. DNA Res 16:73-80
Masui, Shinji; Ohtsuka, Satoshi; Yagi, Rika et al. (2008) Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells. BMC Dev Biol 8:45
Sharov, Alexei A; Masui, Shinji; Sharova, Lioudmila V et al. (2008) Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data. BMC Genomics 9:269
Tsuji, Yukiko; Tsuji, Yukiiko; Yoshimura, Naoko et al. (2008) Maintenance of undifferentiated mouse embryonic stem cells in suspension by the serum- and feeder-free defined culture condition. Dev Dyn 237:2129-38
Carter, Mark G; Stagg, Carole A; Falco, Geppino et al. (2008) An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells. Gene Expr Patterns 8:181-98

Showing the most recent 10 out of 31 publications