Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis

Susan Chung, Petras P Dzeja, Randolph S. Faustino, Andre Terzic

Research output: Chapter in Book/Report/Conference proceedingConference contribution

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages254-263
Number of pages10
Volume1147
DOIs
StatePublished - Dec 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1147
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Creatine Kinase
Stem cells
Stem Cells
MM Form Creatine Kinase
Sarcolemma
Embryonic Stem Cells
Embryoid Bodies
Actinin
MB Form Creatine Kinase
Mitochondria
Myofibrils
Cardiac Myocytes
Dimers
Energy Metabolism
Machinery
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Proteins
Wire

Keywords

  • Differentiation
  • Embryonic stem cells
  • Energetic communication
  • Mitochondria
  • Phosphotransfer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chung, S., Dzeja, P. P., Faustino, R. S., & Terzic, A. (2008). Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. In Annals of the New York Academy of Sciences (Vol. 1147, pp. 254-263). (Annals of the New York Academy of Sciences; Vol. 1147). https://doi.org/10.1196/annals.1427.004

Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. / Chung, Susan; Dzeja, Petras P; Faustino, Randolph S.; Terzic, Andre.

Annals of the New York Academy of Sciences. Vol. 1147 2008. p. 254-263 (Annals of the New York Academy of Sciences; Vol. 1147).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Chung, S, Dzeja, PP, Faustino, RS & Terzic, A 2008, Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. in Annals of the New York Academy of Sciences. vol. 1147, Annals of the New York Academy of Sciences, vol. 1147, pp. 254-263. https://doi.org/10.1196/annals.1427.004
Chung S, Dzeja PP, Faustino RS, Terzic A. Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. In Annals of the New York Academy of Sciences. Vol. 1147. 2008. p. 254-263. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1427.004
Chung, Susan ; Dzeja, Petras P ; Faustino, Randolph S. ; Terzic, Andre. / Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. Annals of the New York Academy of Sciences. Vol. 1147 2008. pp. 254-263 (Annals of the New York Academy of Sciences).
@inproceedings{34b96566c8f74b6f93e0431fd8039ce0,
title = "Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis",
abstract = "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.",
keywords = "Differentiation, Embryonic stem cells, Energetic communication, Mitochondria, Phosphotransfer",
author = "Susan Chung and Dzeja, {Petras P} and Faustino, {Randolph S.} and Andre Terzic",
year = "2008",
month = "12",
doi = "10.1196/annals.1427.004",
language = "English (US)",
isbn = "9781573317139",
volume = "1147",
series = "Annals of the New York Academy of Sciences",
pages = "254--263",
booktitle = "Annals of the New York Academy of Sciences",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=57649217415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57649217415&partnerID=8YFLogxK

U2 - 10.1196/annals.1427.004

DO - 10.1196/annals.1427.004

M3 - Conference contribution

C2 - 19076447

AN - SCOPUS:57649217415

SN - 9781573317139

VL - 1147

T3 - Annals of the New York Academy of Sciences

SP - 254

EP - 263

BT - Annals of the New York Academy of Sciences

ER -