Innovative Technique Produces More Reliable Pluripotent Stem Cells

Induced pluripotent stem cells are commonly generated by transduction of the "OSKM" genes into cells for the production of the reprogramming factors Oct4 (octamer-binding transcription factor 4), Sox2 (sex determining region Y)-box 2), Klf4 (Krueppel-like factor 4), and Myc (v-myc myelocytomatosis viral oncogene homolog protein). Although such iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation.

Investigators at the Hebrew University of Jerusalem (Israel) used bioinformatic analysis to design a new formulation of transducer genes that generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. The new cocktail of reprogramming factors (SNEL) included Sall4 (Sal-like protein 4), Nanog (Nanog homeobox), Esrrb (Estrogen-related receptor beta), and Lin28 (Lin-28 homolog A).

The new SNEL cocktail created fewer iPSC colonies than the traditional OSKM approach, but approximately 80% of those produced passed the most stringent pluripotency tests. This is preferable to the OSKM method, which produces a large number of colonies, but the majority of which fail the pluripotency tests.

First author Dr. Yossi Buganim, a postdoctoral researcher in developmental biology at the Hebrew University of Jerusalem, said, "SNEL may reprogram cells better than OSKM because it does not rely on the master regulators Oct4 and Sox2, which might activate part of the adult cell genome. This research demonstrates the effectiveness of bioinformatics tools in producing high quality iPSCs."

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Hebrew University of Jerusalem