Peering Into The iPS Black Box

An ambitious project has tracked the epigenetic, transcriptional and proteomic changes that occur during the formation of induced pluripotent stem cells.

AsianScientist (Dec. 17, 2014) – Although using Yamanaka factors to obtain induced pluripotent stem cells (iPS) is now a well-established method, little is known about the mechanism driving the dramatic reprogramming. Project Grandiose, an international consortium including researchers from Korea and Australia, has now published five papers in Nature and Nature Communications detailing the epigenetic, transcriptional and proteomic changes involved.

The findings are a major advance in stem cell science and could help usher in a new era of regenerative medicine, where a small sample of a patient’s cells could be used to grow new tissues and organs for transplant.

“The race is on to make reprogramming a safe and efficient process so that the resulting stem cells can be broadly applied in therapies,” said Professor Thomas Preiss from the Austrialian National University (ANU) and lead author on the paper focused on miRNAs.

“We have described in unprecedented detail the molecular changes that cells undergo as they reprogram into stem cells and also discovered a new kind of pluripotent cell that can be seen as a prototype for therapeutic cell production.”

Called F-class cells, after the fuzzy appearance of the cell colonies in culture, the newly described pluripotent cells were obtained by maintaining reprogramming factor levels at elevated levels.

“The new type of stem cell we identified and characterized is easier to grow and manipulate, which will aid in drug screening efforts and disease modelling in the laboratory,” Preiss said.

“The published papers represent a global effort to describe changes in different types of cellular macromolecules during reprogramming and to relate patterns across different layers of gene regulation. However, there is much more to be discovered and further explored in the datasets, which are now publicly available through, the collaboration platform of Stem Cells Australia.”

The data will now be used around the world by researchers working on reprogramming, stem cells, cancer, fetal development and regenerative medicine.

The articles can be found at:
Hussein et al. (2014) Genome-Wide Characterization of the Routes to Pluripotency.
Tonge et al. (2014) Divergent Reprogramming Routes Lead to Alternative Stem-cell States.
Clancy et al. (2014) Small RNA Changes en route to Distinct Cellular States of Induced Pluripotency.
Benevento et al. (2014) Proteome Adaptation in Cell Reprogramming Proceeds via Distinct Transcriptional Networks.
Lee et al. (2014) An Epigenomic Roadmap to Induced Pluripotency Reveals DNA Methylation as a Reprogramming Modulator.


Source: Australian National University.
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