Biomedical subjects

Masayuki Usuda

Publications and source records attributed to Masayuki Usuda.

3 recordsLinked to original sources

PubMed2006

GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal. In this study, we searched for molecules downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat binding protein (GABP) alpha. Expression of GABPalpha was restricted to undifferentiated ES cells and controlled by STAT3. We found that the expression level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand, GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4 repressors.

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PubMed2005

Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal.

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PubMed2002

Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity.

Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.

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