title: Energy metabolism plasticity enables stemness programs.
abstract: Engineering pluripotency through nuclear reprogramming and directing stem cells into defined lineages underscores cell fate plasticity. Acquisition of and departure from stemness are governed by genetic and epigenetic controllers, with modulation of energy metabolism and associated signaling increasingly implicated in cell identity determination. Transition from oxidative metabolism, typical of somatic tissues, into glycolysis is a prerequisite to fuel-proficient reprogramming, directing a differentiated cytotype back to the pluripotent state. The glycolytic metabotype supports the anabolic and catabolic requirements of pluripotent cell homeostasis. Conversely, redirection of pluripotency into defined lineages requires mitochondrial biogenesis and maturation of efficient oxidative energy generation and distribution networks to match demands. The vital function of bioenergetics in regulating stemness and lineage specification implicates a broader role for metabolic reprogramming in cell fate decisions and determinations of tissue regenerative potential.
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Clifford D L
authors.initials: CDL
authors.lastname: Folmes
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Petras P
authors.initials: PP
authors.lastname: Dzeja
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D004734:Energy Metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods / Q000639:trends