Metabolic determinants of embryonic development and stem cell fate

Abstract

Decoding stem cell metabolism has implicated a tight linkage between energy metabolism and cell fate regulation, a dynamic interplay vital in the execution of developmental and differentiation programs. The inherent plasticity in energy metabolism enables prioritization of metabolic pathways in support of stage-specific demands. Beyond traditional support of energetic needs, intermediate metabolism may also dictate cell fate choices through regulation of cellular signaling and epigenetic regulation of gene expression. The notion of a “metabolism-centric” control of stem cell differentiation has been informed by developmental embryogenesis based upon an on-demand paradigm paramount in defining diverse developmental behaviors, from a post-fertilization nascent zygote to complex organogenesis leading to adequate tissue formation and maturation. Monitored through natural or bioengineered stem cell surrogates, nutrient-responsive metabolites are identified as mediators of cross-talk between metabolic flux, cell signaling, and epigenetic regulation charting, collectively, whether a cell will self-renew to maintain progenitor pools, lineage specify to ensure tissue (re)generation or remain quiescent to curb stress damage. Thus, bioenergetics are increasingly recognized as integral in governing stemness and associated organogenic decisions, paving the way for metabolism-defined targets in control of embryology, stem cell biology and tissue regeneration.

Association between p53 Arg72Pro polymorphism and recurrent pregnancy loss: an updated systematic review and meta-analysis

“…For normal embryonic development during pregnancy, it is crucial for the embryo to achieve trophoblastic proliferation to an appropriate extent and induce its own blood supply by adequate angiogenesis once implanted (Dimitriadis et al, 2005;Folmes and Terzic, 2014). Therefore, angiogenesis, apoptosis, or both, play important roles in cytotrophoblasts or blood vessels and the dysfunction can lead to imbalances of cell differentiation and occurrence of spontaneous abortion (Plaisier, 2011).…”

Concise Review: Energy Metabolites: Key Mediators of the Epigenetic State of Pluripotency

“…Pluripotent stem cells (PSC), either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC), constitute a prominent model for cell self-renewal and differentiation and for the study of cellular events that are involved in early differentiation. The roles of specific metabolic processes, especially aerobic glycolysis, in stem cell plasticity have been suggested by several recent studies [5][6][7][8][9][10][11][12][13]. Despite the profound insights provided by recent studies and extensive efforts in the field, the role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood [11,14].…”

Erythroid differentiation displays a peak of energy consumption concomitant with glycolytic metabolism rearrangements

“…It has been demonstrated that stem cells tend to 7 switch from glycolytic metabolism toward mitochondrial oxidative phosphorylation 8 (OXPHOS) while they differentiate [3][4][5]. Accordingly, it was suggested that a balance 9 between glycolysis and OXPHOS metabolism could somehow guide the choice between 10 self-renewal and differentiation in stem cells fate [6]. It has also been demonstrated that 11 preventing the shutting down of the glycolytic pathway was detrimental for neuronal 12 differentiation [4].…”