TY - GEN
T1 - Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis
AU - Chung, Susan
AU - Dzeja, Petras P.
AU - Faustino, Randolph S.
AU - Terzic, Andre
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2008/12
Y1 - 2008/12
N2 - Differentiation of pluripotent low-energy requiring stem cells into the high-energy expenditure cardiac lineage requires coordination of genomic programming and energetic system maturation. Here, in a murine embryonic stem cell cardiac differentiation model, emergence of electrical and beating activity in cardiomyocytes developing within embryoid bodies was coupled with the establishment of the mitochondrial network and expansion of the creatine kinase (CK) phosphotransfer system. Stem cell cardiogenesis was characterized by increased total CK activity, an isoform shift manifested by amplified muscle CK-M mRNA levels and protein content, and the appearance of cardiac-specific CK-MB dimers. Treatment of differentiating stem cells with BMP2, a cardiogenic growth factor, promoted CK activity. CK-M clustered around developing myofibrils, sarcolemma, and the perinuclear compartment, whereas CK-B was tightly associated with myofibrillar α-actinin, forming wire-like structures extending from the nuclear compartment to the sarcolemma. Developmentally enhanced phosphotransfer enzyme-anchoring protein FHL2 coalesced the myofibrillar CK metabolic signaling circuit, providing an energetic continuum between mitochondria and the nascent contractile machinery. Thus, the evolving CK-catalyzed phosphotransfer network integrates mitochondrial energetics with cardiogenic programming, securing the emergence of energy-consuming cardiac functions in differentiating embryonic stem cells.
AB - Differentiation of pluripotent low-energy requiring stem cells into the high-energy expenditure cardiac lineage requires coordination of genomic programming and energetic system maturation. Here, in a murine embryonic stem cell cardiac differentiation model, emergence of electrical and beating activity in cardiomyocytes developing within embryoid bodies was coupled with the establishment of the mitochondrial network and expansion of the creatine kinase (CK) phosphotransfer system. Stem cell cardiogenesis was characterized by increased total CK activity, an isoform shift manifested by amplified muscle CK-M mRNA levels and protein content, and the appearance of cardiac-specific CK-MB dimers. Treatment of differentiating stem cells with BMP2, a cardiogenic growth factor, promoted CK activity. CK-M clustered around developing myofibrils, sarcolemma, and the perinuclear compartment, whereas CK-B was tightly associated with myofibrillar α-actinin, forming wire-like structures extending from the nuclear compartment to the sarcolemma. Developmentally enhanced phosphotransfer enzyme-anchoring protein FHL2 coalesced the myofibrillar CK metabolic signaling circuit, providing an energetic continuum between mitochondria and the nascent contractile machinery. Thus, the evolving CK-catalyzed phosphotransfer network integrates mitochondrial energetics with cardiogenic programming, securing the emergence of energy-consuming cardiac functions in differentiating embryonic stem cells.
KW - Differentiation
KW - Embryonic stem cells
KW - Energetic communication
KW - Mitochondria
KW - Phosphotransfer
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U2 - 10.1196/annals.1427.004
DO - 10.1196/annals.1427.004
M3 - Conference contribution
C2 - 19076447
AN - SCOPUS:57649217415
SN - 9781573317139
T3 - Annals of the New York Academy of Sciences
SP - 254
EP - 263
BT - Mitochondria and Oxidative Stress in Neurodegenerative Disorders
PB - Blackwell Publishing Inc.
ER -