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Pluripotency and differentiation control mechanisms in mouse ES cells

Gene regulatory networks acting downstream of Wnt/β-catenin pathway

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Graduate School of Engineering / Faculty of Engineering
2013/04/01

‘Pluripotent cells’ that have the ability to differentiate into a variety of organs and tissues develop during the early phase of embryogenesis. Embryonic stem (ES) cells are derived from this population of cells. Wnt family proteins, a group of proteins that are highly conserved between invertebrates and vertebrates and have a variety of roles during organogenesis, and are also involved in the maintenance of pluripotency in mouse ES cells. The mechanisms underlying the paradoxical roles of Wnts have yet to be elucidated.

An example of a region where bindings of β-catenin, Oct4, Sox2, Nanog, and Tcf3 overlap on the genomic DNA of mouse ES cells ©Shinsuke Ohba
Binding of each factor is supposed to occur in between red and blue peaks (shown as the yellow region). Bindings of β-catenin, Oct4, Sox2, Nanog, and Tcf3 overlap in the Pou5f1 (Oct4) gene region; the sequence of the region is highly conserved between mammals (bottom).

Project Associate Professor Shinsuke Ohba (The University of Tokyo Graduate School of Engineering, Department of Bioengineering), collaborating with Drs. Andrew P. McMahon (Director and Professor, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at University of South California) and X. Shirley Liu (Associate Professor, Dana-Farber Cancer Institute, Harvard School of Public Health), found that the Wnt/β-catenin pathway uses distinct gene regulatory networks in the regulation of pluripotency and differentiation in mouse ES cells.

This finding will contribute to the understanding of molecular basis of pluripotency and differentiation of ES cells and to the development of safer and more appropriate strategies for the use of stem cells in regenerative medicine.

Press release

Paper

Xiaoxiao Zhang, Kevin A. Peterson, X. Shirley Liu, Andrew P. McMahon, and Shinsuke Ohba,
“Gene regulatory networks mediating canonical Wnt signal directed control of pluripotency and differentiation in embryo stem cells”,
Stem Cells Online Edition: 2013/3/15. doi: 10.1002/stem.1371.
Article link

Links

Graduate School of Engineering

Department of Bioengineering, Graduate School of Engineering

Skeletal Development and Regeneration Research Group, Graduate School of Medicine

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