Metabolic decisions in development and disease—a Keystone Symposia report

Abstract

There is an increasing appreciation for the role of metabolism in cell signaling and cell decision making. Precise metabolic control is essential in development, as evident by the disorders caused by mutations in metabolic enzymes. The metabolic profile of cells is often cell‐type specific, changing as cells differentiate or during tumorigenesis. Recent evidence has shown that changes in metabolism are not merely a consequence of changes in cell state but that metabolites can serve to promote and/or inhibit these changes. Metabolites can link metabolic pathways with cell signaling pathways via several mechanisms, for example, by serving as substrates for protein post‐translational modifications, by affecting enzyme activity via allosteric mechanisms, or by altering epigenetic markers. Unraveling the complex interactions governing metabolism, gene expression, and protein activity that ultimately govern a cell's fate will require new tools and interactions across disciplines. On March 24 and 25, 2021, experts in cell metabolism, developmental biology, and human disease met virtually for the Keystone eSymposium, “Metabolic Decisions in Development and Disease.” The discussions explored how metabolites impact cellular and developmental decisions in a diverse range of model systems used to investigate normal development, developmental disorders, dietary effects, and cancer‐mediated changes in metabolism.

PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development

“…A growing body of evidence suggests that metabolic enzymes and metabolites can alter the epigenome and gene expression during development ( Li et al, 2018 ; Miyazawa & Aulehla, 2018 ; Cable et al, 2021 ). PARP-1 may be a key factor in regulating the reciprocal relationship between metabolism and gene regulation during development.…”

Trans- and Multigenerational Maternal Social Isolation Stress Programs the Blood Plasma Metabolome in the F3 Generation

“…Because the orchestrated regulation of metabolic pathways is essential for stress regulation, development, and successful aging, its failure may lead to cell and tissue dysfunction and result in chronic and non-communicable diseases. On the other hand, metabolic profiles are often cell-type specific [ 78 ], thus providing an opportunity for the discovery of causal pathogenic mechanisms and early diagnosis of a disease. Due to the potentially significant health impact of social isolation, understanding the metabolic consequences of ancestral stress may provide new personalized therapeutic strategies to mitigate stress-associated adverse health outcomes.…”

Functions of LKB1 in neural crest development: The story unfolds

“…Little is known about the metabolic requirements during NCC formation, although energy metabolism is a central driver of stem cell fate 92 . Measurements of oxygen consumption by trunk explants from amphibians showed that oxygen uptake by NCCs increases when cells begin to differentiate into melanocytes, 93 suggesting that metabolic pathways contribute to the early steps of neural crest formation.…”

“…Little is known about the metabolic requirements during NCC formation, although energy metabolism is a central driver of stem cell fate. 92 Measurements of oxygen consumption by trunk explants from amphibians showed that oxygen uptake by NCCs increases when cells begin to differentiate into melanocytes, 93 suggesting that metabolic pathways contribute to the early steps of neural crest formation. After this early study conducted in the 1940s, metabolic studies were long neglected and only recently has there once again been renewed interest in the metabolic contribution to neural crest cell fate.…”