title: Aged iPSCs display an uncommon mitochondrial appearance and  fail to undergo in vitro neurogenesis.
abstract: Reprogramming of human fibroblasts into induced pluripotent stem cells (iPSCs) leads to mitochondrial rejuvenation, making iPSCs a candidate model to study the mitochondrial biology during stemness and differentiation. At present, it is generally accepted that iPSCs can be maintained and propagated indefinitely in culture, but no specific studies have addressed this issue. In our study, we investigated features related to the 'biological age' of iPSCs, culturing and analyzing iPSCs kept for prolonged periods in vitro. We have demonstrated that aged iPSCs present an increased number of mitochondria per cell with an altered mitochondrial membrane potential and fail to properly undergo in vitro neurogenesis. In aged iPSCs we have also found an altered expression of genes relevant to mitochondria biogenesis. Overall, our results shed light on the mitochondrial biology of young and aged iPSCs and explore how an altered mitochondrial status may influence neuronal differentiation. Our work suggests to deepen the understanding of the iPSCs biology before considering their use in clinical applications.
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Celluzzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Ginevra
authors.initials: G
authors.lastname: Zanni
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D063269:Mitochondrial Turnover / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D055495:Neurogenesis / Q000235:genetics; D010641:Phenotype; D013997:Time Factors; D014162:Transfection