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Molecular alliance that sustains embryonic stem cell state
Date:3/4/2008

One of the four ingredients in the genetic recipe that scientists in Japan and the U.S. followed last year to persuade human skin cells to revert to an embryonic stem cell state, is dispensable in ES cells, thanks to the presence of a molecular alliance between a specific group of key proteins known as transcription factors, a research team led by the Genome Institute of Singapore (GIS) under the Agency for Science, Technology and Research (A*STAR) reports in the current issue of Nature Cell Biology.

The reprogramming factor - Klf4, one of the transcription factors that determine whether a cell's genes are active or silent - has at least two other sibling molecules that will substitute Klf4 to maintain a pluripotent embryonic stem (ES) cell state, the GIS-led team said.

Klf4 (also known as gut-enriched Krppel-like factor or Gklf) belongs to the Krppel-like factor (Klf) family of transcription factors that regulate numerous biological processes including proliferation, differentiation, development and apoptosis, or programmed cell death.

Since reprogramming mature cells to the ES state may provide a ready source of tissue for biomedical research and clinical treatment of diseases such as Parkinson's and diabetes, several laboratories, including GIS, are trying to better understand and finely tune the reprogramming process.

The team looks for clues for what these reprogramming ingredients are doing in ES cells.

"Klf4 has been a mysterious player among the four reprogramming factors. As taking out Klf4 in ES cells did not have any apparent effects, it is difficult to reconcile why such a potent reprogramming factor has no role in ES cell biology," said GIS scientist Ng Huck Hui, Ph.D., who headed the research team. Other members of the team include researchers from the National University of Singapore and University of Illinois at Urbana-Champaign.

The GIS research team found that when Klf4 was depleted, Klf
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Contact: Cathy Yarbrough
sciencematter@yahoo.com
858-243-1814
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

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