Journal article

Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells

Jarmon G Lees, David K Gardner, Alexandra J Harvey

DEVELOPMENT | COMPANY BIOLOGISTS LTD | Published : 2018

Abstract

As human pluripotent stem cells (hPSCs) exit pluripotency, they reportedly switch from glycolytic energy production to primarily mitochondrial metabolism. Here, we show that upon ectoderm differentiation to neural precursor cells (NPCs), hPSCs increase glycolytic rate, ultimately producing more carbon as lactate than is consumed as glucose. However, glucose, lactate and pyruvate utilization decrease to half their PSC levels by the NPC stage, establishing a more quiescent metabolic state. Furthermore, we characterize a metabolic exit event within the first 24 h of differentiation, plausibly necessary to transition hPSCs out of the pluripotent state. Contrary to current thinking, mitochondrial..

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Grants

Awarded by Australian Research Council Special Research Initiative Stem Cells Australia


Awarded by Jasper Loftus-Hills Award


Awarded by Alfred Nicholas Fellowship Award


Awarded by F. H. Drummond Travel Award


Funding Acknowledgements

This work was supported by the Australian Research Council Special Research Initiative Stem Cells Australia (SR110001002), and a Jasper Loftus-Hills Award (UTR7.116), an Alfred Nicholas Fellowship Award (UTR6.197), and an F. H. Drummond Travel Award (UTR6.184) from the University of Melbourne.