In the new issue of the journal Cell Stem Cell, Singapore
scientists report the surprising discovery that a novel transcription
factor, Nr5a2, can replace one of the classical reprogramming factors,
Oct4, to significantly increase the efficiency of reprogramming
differentiated stem cells into induced pluripotent stem cells (iPS
Previous research revealed that the reprogramming of differentiated
cells into induced iPS cells could be achieved by the three
transcription factors, Oct4, Sox2 and Klf4.
In this latest finding, which is potentially relevant to cell
therapy-based medicine, Genome Institute of Singapore (GIS) and National
University of Singapore (NUS) scientists determined that Nr5a2 can
replace Oct4. Thus, a new combination of Nr5a2, Sox2 and Klf4 can
reprogram differentiated cells into iPS cells.
"This is a very exciting moment," said GIS Senior Group Leader Ng
Huck Hui, Ph.D. "Fundamental research in embryonic stem cells is
extremely important for us to harness the full potentials of these
cells, and this study provides valuable and crucial insights into the
mechanism of reprogramming.
"Given Oct4’s critical role in embryonic stem cells and
reprogramming, we were very surprised with the discovery that Nr5a2
could replace Oct4," added Dr. Ng, senior author of the paper. "This
study highlights the prospect of finding more surprises in the field of
"This paper represents significant addition to the very active field
of cellular reprogramming," added Davor Solter, M.D., Ph.D., Senior
Principal Investigator at Singapore’s Institute of Medical Biology
Both GIS and IMB are part of Singapore’s A*STAR (Agency for Science,
Technology and Research).
"The authors show that gene coding for nuclear receptor Nr5a2 can
replace one of the classical reprogramming factors Oct 4," Dr. Solter
said. "In addition they presented evidence that this and another nuclear
receptor can significantly increase the efficiency of reprogramming.
These results have great basic and practical significance."
The reprogramming of differentiated cells into iPS cells is one of
the most important breakthroughs in stem cell research, because iPS
cells can give rise to all other differentiated cell types that make up
the human body.
Because they behave like embryonic stem cells, iPS cells are
important starting points for the creation of organs for replacement or
The Cell Stem Cell paper, published on Jan. 21, 2010, is the
second research report on iPS cell science by Dr. Ng’s research group.
In Jan. 2009, Dr. Ng and his colleagues reported in Nature Cell
Biology that the transcription factor Esrrb could replace Klf4 in
the combination of Oct4, Sox2 and Klf4 for iPS cell creation.