A*Star research throws light on stem cell differentiation

Updated on 14 March 2013

Scientists at the Agency for Science, Technology and Research'sGenome Institute of Singapore have discovered that key gene regulators work in pairs to trigger stem cells to differentiate into specific cell types

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The study has discovered that it takes a pair of transcription factors to orchestrate key decisions in embryo development

Singapore: Scientists at the Agency for Science, Technology and Research's (A*STAR) Genome Institute of Singapore (GIS) have discovered that key gene regulators work in pairs to trigger stem cells to differentiate into specific cell types. Furthermore, they showed that selective partnering of the regulators result in uniquely specified developmental outcomes.

An embryo develops from a single cell to a complex, interconnected assemblage of multiple cell types in the adult organism, such as the muscles, nerves, lungs and heart. The fates of embryonic cells as they differentiate into specialized adult cells require tightly regulated expression of hundreds of genes; each cell type being regulated by a unique and specific pattern of gene expression. Transcription factors are master regulators of gene expression and have been implicated as key players in the appropriate specification embryo development. They do this by binding to DNA thereby "turning on" or "turning off" nearby genes. What is less clear is how these transcription factors select specific sets of genes for activation and repression.

A recent study by scientists from GIS has discovered that it takes a pair of transcription factors, working tightly together, to orchestrate key decisions in embryo development. The discovery was published in the prestigious EMBO Journal.

The study, a multidisciplinary collaborative effort, established that the transcription factor Oct4 alternatively partners with two related factors, Sox2 or Sox17. This paper, together with a related paper published in the journal Stem Cells in 2011 ("Conversion of Sox17 into a reprogramming factor by re-engineering its association with Oct4 on DNA."), makes a key discovery about how the selective partnering of the two transcription factors can lead to very different developmental outcomes.

Lead author Dr Lawrence Stanton said, "This work was a unique collaboration between scientists hailing from different areas of expertise - computational biology, cell biology, developmental biology and biochemistry. The unique line of research was only possible by the interdisciplinary efforts of these scientists."

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