Metabolic regulation in pluripotent stem cells

Effect of Donor Age and Liver Steatosis on Potential of Decellularized Liver Matrices to be used as a Platform for iPSC‐Hepatocyte Culture

“…[31] They also showed that oleate exposure along with SCD1 inhibitor rescued the endodermal differentiation. Along with this report, the well-known role of fatty acids in regulating iPSC differentiation [32] can potentially explain the increase in endodermal marker expression in high steatosis hDLM since this matrix contains the highest fat content. At the HS stage of differentiation, we did not observe the same pattern.…”

Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential

“…Cell metabolism is known to play a significant role in the production of energy, cell-fate determination, and stem cell activity in different contexts [ 46 , 47 ]. Accordingly, the first set of activated genes during cell reprogramming corresponds to genes involved in increased proliferation and metabolic remodeling.…”

“…Oxidative phosphorylation is used by somatic cells for energy production, but during cell reprogramming, the transition to pluripotency is accompanied by a shift to glycolytic metabolism, and in fact, the efficiency of cell reprogramming is significantly enhanced by raising glucose concentrations in the culture medium [ 49 , 50 ]. It should also be noted that many components of the core pluripotency factor network crucially regulate cellular metabolism [ 46 , 51 ]. For instance, the well-studied core pluripotency factors OCT4 and CMYC regulate glycolysis directly by targeting key glycolytic enzymes in ESCs, such as HK2 and PKM2, which affect lactate, acetate, and glucose metabolites.…”

“…For instance, the well-studied core pluripotency factors OCT4 and CMYC regulate glycolysis directly by targeting key glycolytic enzymes in ESCs, such as HK2 and PKM2, which affect lactate, acetate, and glucose metabolites. CMYC also regulates metabolic gene targets, influencing glycolysis, mitochondrial biogenesis, and glutamine and proline catabolism, among others [ 46 , 52 , 53 ]. The pluripotency core factor LIN28 has also been reported to play a role in regulating metabolism by turning off mitochondrial OXPHOS and enhancing one-carbon metabolism and histone methylation [ 54 ].…”

“…According to these findings, some metabolic intermediates may contribute to the regulation of chromatin accessibility. Several studies place glycolysis as a crucial producer of metabolic intermediates necessary to produce new biomass to sustain cell growth and division and as a source of small organic methyl and acetyl groups required to perform epigenetic changes [ 46 , 52 , 65 , 66 , 67 ]. Research over the last decade has identified essential roles for small organic metabolites in the regulation of epigenetics and transcription, including S-adenosyl methionine (SAM) produced via the one-carbon cycle, Acetyl-CoA from glycolysis, as well as α-ketoglutarate (α-KG), nicotine adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) from the Tricarboxylic Acid Cycle (or TCA cycle) [ 68 , 69 , 70 ].…”