Initially we sought to compare the in vivo engraftment potential of hematopoietic stem cells derived from fESC, ntESC, and iPSC in a mouse model of thalassemia. However, even in vitro we observed strikingly different blood-forming potential; thus, we focused here instead on understanding this phenomenon. Our initial set of pluripotent stem cells were derived from the hybrid C57BL/6 x CBA (B6/CBAF1) strain carrying a deletion in the beta-globin locus15, which is otherwise irrelevant to this study (Fig. 1a). We isolated fESC cells from naturally fertilized embryos and derived ntESC cells from nuclei of dermal fibroblasts8. We infected early bone marrow cells (Kit+, Lin−, CD45+) or dermal fibroblasts from aged mice with retroviral vectors carrying Oct4, Sox2, Klf4, and Myc, and selected blood-derived and fibroblast-derived iPSC colonies (B-iPSC, F-iPSC). Hematopoietic progenitors and fibroblasts yielded a comparable frequency of reprogrammed colonies (0.02%), which consistent with prior reports5, was lower than the yield from fibroblasts of a juvenile mouse (0.1%). We characterized the fESC, ntESC, and iPSC lines for expression of Oct4 and Nanog by immunohistochemistry, and demonstrated multi-lineage differentiation potential in teratomas
