Souped-up method for iPS cell reprogramming

Peng Jin and collaborators led by Da-Hua Chen from the Institute of Zoology, Chinese Academy of Sciences have a new paper in Stem Cell Reports. They describe a souped-up method for producing iPS cells (induced pluripotent stem cells).

Production of iPS cells in the laboratory is becoming more widespread. Many investigators, including those at Emory, are using the technology to establish “disease in a dish” models and derive iPS cells from patient donations, turning them into tools for personalized medicine research.

The new report from Jin and his colleagues is not a radical change* from previous efforts that follow in the footsteps of Shinya Yamanaka, who received a Nobel Prize in 2012 for the discovery of the original method. This technique still uses retroviruses to introduce four transcription factor genes (Oct4, Sox2, Nanog and Klf4) into fibroblast cells, which reprogram some of the Maglie Calcio fibroblasts and convert them into iPS cells. Basically, these are genes whose activities drive and determine stem cell character. If you turn them all on, the cell reprograms.

What’s distinctive in the paper from Jin and colleagues is that three of the transcription factors were artificially enhanced in potency, making iPS cell generation more efficient and faster.

The authors also demonstrate how intimately the Tet enzymes are involved in iPS cell reprogramming, physicially associating with two of the four stem cell driver factors. Tet enzymes are responsible for tweaking epigenetic marks on DNA, so that maglie calcio poco prezzo methylation markers that say “this gene is shut off” instead say “ready to turn on.”

Jin has been a pioneer in defining the biology of the epigenetic marks (5-hydroxymethylcytosine or 5-hmC is the most prominent) imposed by the Tet enzymes. One recent example was his team’s demonstration — in collaboration with Stephen Dalton at UGA — that levels of 5-hmC oscillate during the cell cycle in embryonic stem cells and almost disappear during DNA replication.

*Some innovation has gone into replacing potentially oncogenic retroviruses with proteins. Also, one recent report suggested that a simpler approach – exposing cells to acidic or other stressful conditions – was sufficient for reprogramming, but that paper is now being questioned.

Posted on by Quinn Eastman in Cancer, Immunology, Neuro Leave a comment

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Quinn Eastman

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