Abstract
We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.
Highlights
The development by the Yamanaka group of a method to reprogram somatic cells into induced pluripotent stem cells by over expression of pluripotency factors hold considerable promises for the development of stem cell therapies [1,2,3,4,5]
Three somatic cell types were used: embryonic mesenchymal stem cells that were previously derived from hESC [31,32], fetal liver mesenchymal stem cells and adult skin fibroblasts that were derived in our lab
To ascertain that these cells were reprogrammed to a pluripotent state, we first tested them by flow cytometry using a panel of antibodies that are known to be expressed at high levels in hESC [33]
Summary
The development by the Yamanaka group of a method to reprogram somatic cells into induced pluripotent stem cells (iPS) by over expression of pluripotency factors hold considerable promises for the development of stem cell therapies [1,2,3,4,5]. The differentiation potential of iPS has been tested by chimera formation followed by germ line transmission [6,7,8] and more recently by tetraploid complementation [9,10]. These experiments univocally demonstrate that iPS are very similar to embryonic stem cells since both cell types when placed in the blastocyst environment can differentiate into full term mice. One possible approach is to careful examined the in vitro differentiation of iPS into well defined cell types and to compare the results with that of hESC
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