Abstract
BackgroundFor regenerative therapy using induced pluripotent stem cell (iPSC) technology, cell type of origin to be reprogrammed should be chosen based on accessibility and reprogramming efficiency. Some studies report that iPSCs exhibited a preference for differentiation into their original cell lineages, while others did not. Therefore, the type of cell which is most appropriate as a source for iPSCs needs to be clarified.Methodology/Principal FindingsGenetically matched human iPSCs from different origins were generated using bone marrow stromal cells (BMSCs) and dermal fibroblasts (DFs) of the same donor, and global gene expression profile, DNA methylation status, and differentiation properties into the chondrogenic and osteogenic lineage of each clone were analyzed. Although genome-wide profiling of DNA methylation suggested tissue memory in iPSCs, genes expressed differentially in BMSCs and DFs were equally silenced in our bona fide iPSCs. After cell-autonomous and induced differentiation, each iPSC clone exhibited various differentiation properties, which did not correlate with cell-of-origin.Conclusions/SignificanceThe reprogramming process may remove the difference between DFs and BMSCs at least for chondrogenic and osteogenic differentiation. Qualified and genetically matched human iPSC clone sets established in this study are valuable resources for further basic study of clonal differences.
Highlights
The establishment of induced pluripotent stem cells has had a profound impact on both basic biology and clinical medicine. iPSCs were first generated in mice by Takahashi and Yamanaka in 2006 [1], where mouse somatic cells were reprogrammed into pluripotent embryonic stem cell (ESC)-like cells through retroviral infection of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc
It has been reported that bloodderived low-passage mouse iPSCs were less able to differentiate into osteoblasts than mouse ESCs and fibroblast-derived iPSCs [14], and that blood-derived low-passage human iPSCs were less able to differentiate into keratinocytes than human ESCs [15], which suggests that blood-derived iPSCs are not an appropriate source for bone or skin regeneration
OCT3/4, SOX2, KLF4, and c-MYC were introduced with retroviral infection into each cell group at passage 1–2 (BMSCs) and passage 5–7 (DFs) (Figure 1C)
Summary
The establishment of induced pluripotent stem cells (iPSCs) has had a profound impact on both basic biology and clinical medicine. iPSCs were first generated in mice by Takahashi and Yamanaka in 2006 [1], where mouse somatic cells were reprogrammed into pluripotent embryonic stem cell (ESC)-like cells through retroviral infection of four transcription factors, Oct3/4, Sox, Klf, and c-Myc. IPSCs were first generated in mice by Takahashi and Yamanaka in 2006 [1], where mouse somatic cells were reprogrammed into pluripotent embryonic stem cell (ESC)-like cells through retroviral infection of four transcription factors, Oct3/4, Sox, Klf, and c-Myc. The establishment of induced pluripotent stem cells (iPSCs) has had a profound impact on both basic biology and clinical medicine. Several groups reported the successful generation of human iPSCs using similar strategies [3,4,5] Because of their infinite proliferative ability and pluripotent differentiation properties, human iPSCs have been regarded as a promising source for cell-based regenerative therapy. For regenerative therapy using induced pluripotent stem cell (iPSC) technology, cell type of origin to be reprogrammed should be chosen based on accessibility and reprogramming efficiency. The type of cell which is most appropriate as a source for iPSCs needs to be clarified
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