Cell of origin influences molecular and functional properties of murine induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here, we show that iPSCs obtained from fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies (EBs) and different hematopoietic cells. Importantly, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that low-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and ltered differentiation capacity. These observations might affect ongoing attempts to use iPSCs for disease modeling and also could be exploited for potential therapeutic applications to enhance differentiation into desired cell lineages. Keywords: DNA methylation profiling Direct comparison of DNA methylation in iPS cells derived from different tissues