Cell Metabolism Supplemental Information NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism

Supplemental Figures • Fig. S1 (related to Fig. 1). Pathway analysis of proteomics of different liver disease models and validation studies of NANOG target genes identified by NANOG ChIP-seq. • Fig. S2 (related to Fig. 2). Validation of reconstituted bone-marrow-derived cells and Tlr4and Nanog-dependency of mouse TICs isolated from liver tumor model. • Fig. S3 (related to Fig. 3). TLR4 stimulation transactivates NANOG through TAK1 and TBK1-mediated phosphorylation of E2F1 at serines 337 and 332. • Fig. S4 (related to Fig. 4). Silencing of Tlr4 or Nanog promotes basal levels of oxygen consumption rate. • Fig. S5 (related to Fig. 5). NANOG cooperates with PPARs to promote FAO of TICs. • Fig. S6 (related to Fig. 6). Siilencing Nanog promotes glutaminolysis pathway, ATP production and glucose flux in TICs judged by metabolomics analysis, qRT-PCR and stable isotope experiments. • Fig. S7 (related to Fig. 7). Restoration of OXPHOS and/or suppression of FAO reduce the tumor growth and drug resistance.