Table 1.
Summary of application of metabolomics to analyze the effects of culture conditions, drugs, and teratogens on PSCs and PSC-derived cells.
| Effect studied |
Metabolites/pathways affected (Sample type) |
PSC lines | Analytical technique |
Ref. |
|---|---|---|---|---|
| ESC vs. iPSC vs. somatic cells |
Unsaturated fatty acids ↓; SAM ↑, inosine ↑, hypoxanthine ↑ in iPSCs vs. ESCs (intracellular) |
hESCs, mESCs, iPSCs |
LC-MS, GC- MS |
[8,11,28,30] |
| hESCs vs. hECCs |
Octadecenoic acid ↑, glycerol-3- phosphate ↑, 4-hydroxyproline ↑, glutamic acid ↓, mannitol ↓, malic acid ↓, GABA ↓ in hESCs compared to hECCs (intracellular) |
H9 (hESC), NTERA2cl.D1 (hECC) |
GC-MS | [29] |
| Teratogens vs. non- teratogens |
Arginine to asymmetric dimethylarginine (ADMA) between 0.9 and 1.1 for non- teratogens (except for ascorbic acid and caffeine), GABA and malate are increased while succinate is reduced due to teratogens (supernatant) |
H9 (hESC) | LC-MS | [13,38] |
| Ethanol |
Embryoid bodies: MTA ↓ at higher dose and succinyladenosine ↑ at both low and high dose, thyroxine ↑ at lower dose Neural Progenitors: Kynurenine ↑ at lower dose of EtOH Neurons: Indoleacetaldehyde ↑ at lower dose (supernatant) |
H1, H9 (hESCs) |
LC-MS | [41] |
| Steroid hormones |
Estrogen: Lactate ↑, aspartate ↓, lysine ↓, phospholipids ↓, threonine ↓, valine ↓ Testosterone: Glycerol ↑, glycogen ↑, valine ↓ Progesterone: Organic acids ↓, phenylalanine ↓, proline ↓, tyrosine ↓ Common: Glucose ↑ and fatty acids ↓, inositol ↓ in germ-like cells (intracellular) |
BG01 (hESC), IMR90- derived iPSC |
GC-MS | [39] |
| Cisplatin | Oxidized and reduced glutathione ↑, urea ↑, proline ↑, putrescine ↑, spermine ↑, SAM ↑, several nucleotides were also altered (intracellular) |
HM1 (mESC) | NMR, LC- MS |
[40] |
| Passage difference of conditioned media |
Higher lactate, alanine, formate and lower tryptophan in HFF conditioned media which supported hESC maintenance (supernatant) |
H9 (hESC) | NMR | [42] |
| 5% vs. 20% oxygen |
Increased glucose consumption and lactate production at 5% oxygen (supernatant) |
Hues7, Shef3 (hESCs) |
Biochemistry Analyzer |
[45•] |
| 2% oxygen vs. 20% oxygen |
In addition to glycolysis, also utilized glutamine and amino acids for energy generation using oxidative phosphorylation and citric acid cycle (supernatant) |
MEL-2 (hESC) |
HPLC | [44] |
| Lipid and nutrient availability |
Metabolic rewiring takes place depending on nutrient availability and in addition to glycolysis, hPSCs also utilize oxidative phosphorylation (intracellular) |
HUES9, H9 (hESCs), iPS(IMR90)- c4 |
GC-MS | [43••] |
| 2D vs. 3D | Higher lactate-glucose ratios in small hESC colonies than large colonies (supernatant) |
H9 (hESC) | Biochemistry Analyzer |
[46] |
| Passaging methods |
Enzymatic passaging led to reduction of lipogenesis and glucose utilization (intracellular) |
H9 (hESC) | GC-MS | [47] |