000088551 001__ 88551
000088551 005__ 20210902121638.0
000088551 0247_ $$2doi$$a10.1038/s41467-020-15058-6
000088551 0248_ $$2sideral$$a117133
000088551 037__ $$aART-2020-117133
000088551 041__ $$aeng
000088551 100__ $$aBoon, R.
000088551 245__ $$aAmino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines
000088551 260__ $$c2020
000088551 5060_ $$aAccess copy available to the general public$$fUnrestricted
000088551 5203_ $$aPredicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage.
000088551 536__ $$9info:eu-repo/grantAgreement/ES/DGA/FMI048-08
000088551 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000088551 590__ $$a14.919$$b2020
000088551 591__ $$aMULTIDISCIPLINARY SCIENCES$$b4 / 73 = 0.055$$c2020$$dQ1$$eT1
000088551 592__ $$a5.559$$b2020
000088551 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1
000088551 593__ $$aPhysics and Astronomy (miscellaneous)$$c2020$$dQ1
000088551 593__ $$aChemistry (miscellaneous)$$c2020$$dQ1
000088551 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000088551 700__ $$aKumar, M.
000088551 700__ $$aTricot, T.
000088551 700__ $$aElia, I.
000088551 700__ $$0(orcid)0000-0003-3982-1263$$aOrdovas, L.
000088551 700__ $$aJacobs, F.
000088551 700__ $$aOne, J.
000088551 700__ $$aDe Smedt, J.
000088551 700__ $$aEelen, G.
000088551 700__ $$aBird, M.
000088551 700__ $$aRoelandt, P.
000088551 700__ $$aDoglioni, G.
000088551 700__ $$aVriens, K.
000088551 700__ $$aRossi, M.
000088551 700__ $$aVazquez, M.A.
000088551 700__ $$aVanwelden, T.
000088551 700__ $$aChesnais, F.
000088551 700__ $$aEl Taghdouini, A.
000088551 700__ $$aNajimi, M.
000088551 700__ $$aSokal, E.
000088551 700__ $$aCassiman, D.
000088551 700__ $$aSnoeys, J.
000088551 700__ $$aMonshouwer, M.
000088551 700__ $$aHu, W.S.
000088551 700__ $$aLange, C.
000088551 700__ $$aCarmeliet, P.
000088551 700__ $$aFendt, S.M.
000088551 700__ $$aVerfaillie, C.M.
000088551 773__ $$g11 (2020), 1393 [16 pp.]$$pNATURE COMMUNICATIONS$$tNature Communications$$x2041-1723
000088551 8564_ $$s1905366$$uhttps://zaguan.unizar.es/record/88551/files/texto_completo.pdf$$yVersión publicada
000088551 8564_ $$s63842$$uhttps://zaguan.unizar.es/record/88551/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000088551 909CO $$ooai:zaguan.unizar.es:88551$$particulos$$pdriver
000088551 951__ $$a2021-09-02-08:58:16
000088551 980__ $$aARTICLE