Mitochondrial development of the in vitro hepatic organogenesis model with simultaneous cardiac mesoderm differentiation from murine induced pluripotent stem cells

Abstract

Induced pluripotent stem (iPS) cells, resembling embryonic stem (ES) cells in many phenomena, including differentiation potential, colony morphology, and the expression of specific representative markers, were generated from differentiated somatic cells by exogenous expression of several transcriptional factors. In recent, the mitochondria of iPS cells were also reported to be rejuvenated to that of ES cells, however it is not known if the mitochondria have same potential for differentiation as ES cells. We have established the murine ES cell-derived in vitro hepatic organogenesis model, consisting of not only hepatocytes but also endothelial networks together with cardiac mesoderm differentiation, previously. By measuring oxygen concentration and pH in the culture medium, respectively corresponding to the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), we compared the metabolic patterns and bio-energetic profiles of both iPS and ES cells during the hepatic differentiation. The bio-energetic profiles of the in vitro hepatic organogenesis from iPS cells accorded with each differentiation steps, from proliferation stage as the initiation, spontaneously beating cardiac differentiation in the next, and finally liver tissue-formation, as well as that from ES cells. Both iPS and ES cells were differentiated into liver-like tissue with similar mitochondrial development.