Open AccessMitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells
Author(s) -
Jarmon G. Lees,
David K. Gardner,
Alexandra J Harvey
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.168997
Subject(s) - biology , induced pluripotent stem cell , microbiology and biotechnology , neural stem cell , stem cell , human induced pluripotent stem cells , glycolysis , cellular differentiation , mitochondrion , embryonic stem cell , genetics , gene , metabolism , biochemistry
As human pluripotent stem cells (hPSC) exit pluripotency, they reportedly switch from glycolytic energy production to primarily mitochondrial metabolism. Here we show that upon ectoderm differentiation to neural precursor cells (NPC), hPSC increase glycolytic rate, ultimately producing more carbon as lactate than 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 hours of differentiation, plausibly necessary to transition hPSC out of the pluripotent state. Contrary to the current thinking, mitochondrial mass does not increase during NPC induction. Instead, mitochondrial DNA copies and mitochondrial activity decrease suggesting that mitochondrial metabolism either requires suppression, or is not required, for nascent ectoderm differentiation. Our work, therefore, contrasts with the dogma that the hPSC state is primarily glycolytic, transitioning to an oxidative metabolism upon the loss of the pluripotent state. Instead, we show that a heightened glycolytic metabolism is acquired, indicating that metabolic modulation of both glycolysis and mitochondrial metabolism occurs during exit from pluripotency in hPSC.