UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells

Abstract

We wish to clarify that Fig 4A and B intentionally displayed duplicate controls and that the first panel in Figs 1A and S1A was intentionally duplicated.The low (control) and high (FCCP) traces were purposefully duplicated in panels from Fig 4A and B to allow for direct, experimentally unbiased comparisons between the effects of antimycin and sodium oxamate on pluripotent stem and differentiated cells. Panels shown in Fig 4A and B are representative of one single experiment for N = 2 equivalently performed experiments. The panels were separated into parts 4A (antimycin) and 4B (sodium oxamate) for clarity of presentation since the traces and the colors of these traces have overlaps, which makes clear visualization difficult. We apologize for not explicitly stating that these traces were derived from a single, representative experiment.In addition, the first panel in Fig 1A and the first panel of Supplementary Fig S1A were purposefully reproduced to highlight different points. Figure 1A was provided to show how the steady-state pluripotent mitochondrial network appears in relation to the networks shown from three additional pluripotent stem cell lines and one differentiated cell type in the other panels of Fig 1A. Fig S1A was provided to clearly show the progressive effect of a differentiation time course induced by removal of basic fibroblast growth factor over 5 days on the mitochondrial network using a side-by-side comparison with the network in the pluripotent state. We apologize for not explicitly stating that these images were duplicated to highlight these specific, different features.All authors concur with this statement, and we regret not being more explicit in the purposeful use of these duplicated materials in the original publication.

Escherichia coli foster bladder cancer cell line progression via epithelial mesenchymal transition, stemness and metabolic reprogramming

“…The stimulation of the oxidative stress as well as metabolic alteration was also confirmed by the upregulation of a redox sensor protein UCP2. UCP2 (uncoupling proteins) is a mitochondrial inner membrane protein, which transports anion and regulates cell metabolism 10 , 33 . In fact, UCP2 is declined during early tumorigenesis stages to permit increase of ROS level and genomic instability.…”

“…Basically, tumor is portrayed as a homogenous cell population at the initial stages of the tumorigenesis, while during development, various subpopulations generate and cause tumor heterogeneity 9 . Thus, CSC is a small tumor subpopulation with a unique gene signature, which may has the ability to distinguish between papillary and invasive bladder cancer 10 . CSCs possess high plasticity and self-renewal capability that are crucial to expansion and differentiation into all tumor cell types, thus resembling the function of normal stem cells 10 .…”

“…Thus, CSC is a small tumor subpopulation with a unique gene signature, which may has the ability to distinguish between papillary and invasive bladder cancer 10 . CSCs possess high plasticity and self-renewal capability that are crucial to expansion and differentiation into all tumor cell types, thus resembling the function of normal stem cells 10 . Cells with CSCs features possess higher resistance to chemotherapies and cause tumor dormancy 9 .…”

Dietary Micronutrients Promote Neuronal Differentiation by Modulating the Mitochondrial‐Nuclear Dialogue

“…While increased functionality in mature neurons is well supported by data, more equivocal is the possibility that mitochondria also undergo changes in size and morphology with differentiation. Interestingly, while hPSCs would seem to have a similar mitochondrial mass to that of well differentiated fibroblasts, they are relatively underdeveloped and bio‐energetically inactive in hPSCs as mitochondrial uncoupling protein 2 (UCP2) actively exports pyruvate from the mitochondria and blocks entry of pyruvate into the TCA cycle . Furthermore, as hESC and hiPSC differentiate toward a motor neuron fate, mitochondrial mass was found not to change significantly, as determined by measurement of voltage‐dependent anion channel 1 and mitochondrial mass marker‐TOM20 protein expression, although there was a significant increase in levels of mitochondrial electron transfer chain (ETC) proteins .…”

Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming

“…Mitochondrial uncoupling protein 2 (UCP2)-mediated suppression of OXPHOS is required for the maintenance of pluripotency. UCP2 decouples glycolysis from OXPHOS by shunting pyruvate out of the mitochondria [133]. However, it is not completely understood whether this suppression of OXPHOS in PSCs still results in permissive low levels of endogenous ROS.…”