Reprogramming to iPS cells and their subsequent hematopoietic differentiation is more efficient from MEFs than from preB cells

Abstract

Efficiencies of the generation of induced pluripotent stem (iPS) cells from either mouse embryonic fibroblasts (MEF) or from mouse fetal liver (FL) derived preB cells and their hematogenic potencies were compared. In 10 days approximately 2% of the MEFs transduced with Sox-2, Oct-4 and Klf-4 developed to iPS cells, while only 0.01% of transduced FL-preB cells yielded iPS cells, and only after around 3 weeks. Subsequently, the generated iPS cells were induced to differentiate into hematopoietic cells in vitro. On day 5 of differentiation MEF-iPS yielded numbers and percentages of Flk-1+ mesodermal-like cells comparable to those developed from embryonic stem (ES) cells. Compared to ES cells further differentiation to hematopoietic and lymphopoietic cells was reduced, possibly because of persistent expression of the reprogramming factors. By contrast, FL-iPS cells developed lower numbers and percentages of Flk-1+ cells, and no significant further development to hematopoietic or lymphopoietic cells could be induced. These results indicate that the efficiencies of iPS generation and subsequent hematopoietic development depends on the type of differentiated cell from which iPS cells are generated.