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Reprogramming Somatic Cells – Down to One Gene!

From Cell Stem Cell

A new study from the lab of Sheng Ding (The Scripps Research Institute), published recently in Cell Stem Cell, reports the reprogramming of human primary somatic cells using only OCT4 gene transduction and a combination of small molecules. Kim et alhad previously shown than one factor reprogramming is possible, but in human foetal neural stem cells, a cell source perhaps not readily available. iPSCs were generated at an efficiency of roughly 1 colony in 250,000 target cells over an 8 week period utilising neonatal human epidermal keratinocytes (NHEKs). The group also went on to generate iPSCs from human umbilical vein endothelial cells (HUVECs) and amniotic fluid-derived cells (AFDCs). Through a screening process, a novel small molecule activator of 3-phosphoinositide-dependent kinase-1 (PDK1), PS48, was also discovered to be useful in the reprogramming process. It was hypothesised that this small molecule may facilitate a metabolic conversion from mitochondrial oxidation to glycolysis during the reprogramming process, or in other words, metabolically reprogram the cells. The authors note that “differential use of glycolytic metabolism over mitochondrial oxidation by pluripotent cells would favour pluripotency by promoting proliferation/cell cycle transitions with less oxidative stress.”

The correct small molecules are now being identified that can reprogram human primary somatic cells and this represents an important step towards transgene free reprogramming. The obvious next step is to identify small molecules which can replace OCT4 from the reprogramming “cocktail”.

For more see the original paper here and new items from Nature and Eurekalert.