From Pluripotency to Differentiation: The Role of mtDNA in Stem Cell Models of Mitochondrial Diseases

Embryonic stem cells (ESCs) are characterized by pluripotency, self-renewal and unlimited proliferation representing a limitless supply of cells for therapy. Moreover, ESCs represent a unique experimental model to investigate the basic principles of mammalian cell differentiation. ESCs are very useful for in-depth analysis of the development of the mitochondrial complement as the cells activate aerobic metabolism during differentiation. Induced pluripotent stem cells (iPSCs), which are reprogrammed somatic cells, appear to have identical properties to those of ESCs. They will certainly be a fundamental tool to establish human models for specific diseases. Nevertheless, the generation of iPSCs through reprogramming of mouse and human differentiated adult cells containing a mature mitochondrial complement requires a complete reprogramming of the cytoplasm to acquire the “pluripotent” mitochondrial network typical of undifferentiated ESCs.