Figure 1

Effect of culture medium composition on central carbon metabolism of hiPSC-CMs. (A) Representative scheme illustrating the experimental set-up. The metabolome of hiPSC-CMs was evaluated before (d0) and after 10 (d10) and 20 days (d20) of culture in different media: GLCM (black), FAM (Orange), GFAM (Red) and LACM&GFAM (Grey). (B) Heatmap image of metabolome data illustrating specific consumption (blue) and production (red) rates of metabolites (qMET; nmol/(10⁶cell.h)). (C) Ratio of Lac production to Glc consumption (YLac/Glc) in GLCM through culture time. (D) Percentage of labelled M2 isotopomers from [1,2-¹³C]Glc in Lac and in TCA intermediates (Cit, Fum, Mal). (E) Percentage of labelled M4 isotopomers from [U-¹³C]Gln in TCA intermediates. M2 and M4, reflect the first round of TCA cycling of [1,2-¹³C]Glc and [U-¹³C]Gln, respectively. (F) Basal oxygen consumption rate (OCR). (G) Extracellular acidification rate (ECAR). (H) OCR/ECAR ratio reflecting the relative contribution of OXPHOS over glycolysis for energy generation. (I–K) Pie charts indicating the contribution of the main substrates of each media, for TCA cycle pools. The percentages were determined based on the incorporation of each labelled substrate in Cit, Fum and Mal. OA: Oleic Acid and PA: Palmitic acid. Data are represented as mean ± SD of 12–24 wells, n ≥ 3 separate experiments. *p < 0.05; ***p < 0.001; ns, not significant.