TY - UNPB
T1 - Bipotent Liver Progenitors Depend on Glycolysis and Mitochondrial Pyruvate Oxidation for Stem Cell Functions
AU - Schene, Imre Firmin
AU - Ramos, Rúben J.
AU - van Vugt, Anke H.M.
AU - Truong, Hoa
AU - van den Heuvel, Dave J.
AU - Gerritsen, Hans C.
AU - Houtkooper, Riekelt H.
AU - van Weeghel, Michel
AU - Middendorp, Sabine
AU - Mokry, Michal
AU - Spee, Bart
AU - Schneeberger, Kerstin
AU - Nikkels, Peter G.J.
AU - Huch, Meritxell
AU - Clevers, Hans
AU - Nieuwenhuis, Edward E.S.
AU - van Hasselt, Peter M.
AU - Fuchs, Sabine A.
PY - 2020/4/9
Y1 - 2020/4/9
N2 - Aerobic glycolysis, characterized by pyruvate reduction to lactate, serves proliferation in cancer cells and stem cells. To clarify whether this metabolic profile is universal to epithelial stem cells, despite vast differences in physiological turnover rates, we characterized the metabolic phenotype of bipotent liver progenitors (low turnover) relative to intestinal progenitors (high turnover). Using human liver and intestinal organoids, we show high glycolytic fluxes which provide substrates for cellular building blocks and reducing equivalents in proliferating progenitors, compared to their quiescent differentiating counterparts. Similar to cancer and pluripotent stem cells, intestinal progenitors display aerobic glycolysis with pyruvate reduction to lactate to serve their high proliferative demands. Strikingly, liver progenitors combine high glycolysis with substantial mitochondrial oxidation of pyruvate, which they require for both proliferation and maintenance of stemness. This concurs with the anabolic and epigenetic effects of mitochondrial pyruvate oxidation and the homeostatic liver function with low physiological turnover rates.
AB - Aerobic glycolysis, characterized by pyruvate reduction to lactate, serves proliferation in cancer cells and stem cells. To clarify whether this metabolic profile is universal to epithelial stem cells, despite vast differences in physiological turnover rates, we characterized the metabolic phenotype of bipotent liver progenitors (low turnover) relative to intestinal progenitors (high turnover). Using human liver and intestinal organoids, we show high glycolytic fluxes which provide substrates for cellular building blocks and reducing equivalents in proliferating progenitors, compared to their quiescent differentiating counterparts. Similar to cancer and pluripotent stem cells, intestinal progenitors display aerobic glycolysis with pyruvate reduction to lactate to serve their high proliferative demands. Strikingly, liver progenitors combine high glycolysis with substantial mitochondrial oxidation of pyruvate, which they require for both proliferation and maintenance of stemness. This concurs with the anabolic and epigenetic effects of mitochondrial pyruvate oxidation and the homeostatic liver function with low physiological turnover rates.
KW - adult epithelial stem cells
KW - liver progenitor cells
KW - oval cells
KW - proliferation
KW - aerobic glycolysis
KW - Warburg effect
UR - https://www.mendeley.com/catalogue/5e597c15-49f3-3d63-8522-140a3ff384ee/
U2 - 10.2139/ssrn.3564994
DO - 10.2139/ssrn.3564994
M3 - Preprint
T3 - SSRN
BT - Bipotent Liver Progenitors Depend on Glycolysis and Mitochondrial Pyruvate Oxidation for Stem Cell Functions
PB - SSRN
ER -
