TY - JOUR
T1 - Aged iPSCs display an uncommon mitochondrial appearance and fail to undergo in vitro neurogenesis
AU - Masotti, Andrea
AU - Celluzzi, Antonella
AU - Petrini, Stefania
AU - Bertini, Enrico
AU - Zanni, Ginevra
AU - Compagnucci, Claudia
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - In vitro neurogenesis
KW - Induced pluripotent stem cells
KW - Mitochondria
KW - Mitochondrial dysfunction
KW - Stem cell aging
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UR - http://www.scopus.com/inward/citedby.url?scp=84920928909&partnerID=8YFLogxK
M3 - Article
C2 - 25567319
AN - SCOPUS:84920928909
VL - 6
SP - 1094
EP - 1108
JO - Aging
JF - Aging
SN - 1945-4589
IS - 12
ER -