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dc.contributor.authorHogue, A
dc.contributor.authorSivakumaran, P
dc.contributor.authorBond, ST
dc.contributor.authorLing, NXY
dc.contributor.authorKong, AM
dc.contributor.authorScott, JW
dc.contributor.authorBandara, N
dc.contributor.authorHernandez, D
dc.contributor.authorLiu, G-S
dc.contributor.authorWong, RCB
dc.contributor.authorRyan, MT
dc.contributor.authorHausenloy, DJ
dc.contributor.authorKemp, BE
dc.contributor.authorOakhill, JS
dc.contributor.authorDrew, BG
dc.contributor.authorPebay, A
dc.contributor.authorLim, SY
dc.date.accessioned2020-12-18T04:17:00Z
dc.date.available2020-12-18T04:17:00Z
dc.date.issued2018-03-05
dc.identifierpii: 42
dc.identifier.citationHogue, A., Sivakumaran, P., Bond, S. T., Ling, N. X. Y., Kong, A. M., Scott, J. W., Bandara, N., Hernandez, D., Liu, G. -S., Wong, R. C. B., Ryan, M. T., Hausenloy, D. J., Kemp, B. E., Oakhill, J. S., Drew, B. G., Pebay, A. & Lim, S. Y. (2018). Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells. CELL DEATH DISCOVERY, 4 (1), https://doi.org/10.1038/s41420-018-0042-9.
dc.identifier.issn2058-7716
dc.identifier.urihttp://hdl.handle.net/11343/256127
dc.description.abstractHuman induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs are a putative cell source for personalized medicine. Changes in mitochondrial morphology have been shown to occur during cellular reprogramming and pluripotent stem cell differentiation. However, the relationships between mitochondrial dynamics and cardiac mesoderm commitment of iPSCs remain unclear. Here we demonstrate that changes in mitochondrial morphology from a small granular fragmented phenotype in pluripotent stem cells to a filamentous reticular elongated network in differentiated cardiomyocytes are required for cardiac mesodermal differentiation. Genetic and pharmacological inhibition of the mitochondrial fission protein, Drp1, by either small interfering RNA or Mdivi-1, respectively, increased cardiac mesoderm gene expression in iPSCs. Treatment of iPSCs with Mdivi-1 during embryoid body formation significantly increased the percentage of beating embryoid bodies and expression of cardiac-specific genes. Furthermore, Drp1 gene silencing was accompanied by increased mitochondrial respiration and decreased aerobic glycolysis. Our findings demonstrate that shifting the balance of mitochondrial morphology toward fusion by inhibition of Drp1 promoted cardiac differentiation of human iPSCs with a metabolic shift from glycolysis towards oxidative phosphorylation. These findings suggest that Drp1 may represent a new molecular target for future development of strategies to promote the differentiation of human iPSCs into cardiac lineages for patient-specific cardiac regenerative medicine.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells
dc.typeJournal Article
dc.identifier.doi10.1038/s41420-018-0042-9
melbourne.affiliation.departmentCentre for Eye Research Australia (CERA)
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.departmentMedicine (St Vincent's)
melbourne.affiliation.departmentSurgery (St Vincent's)
melbourne.affiliation.departmentOphthalmology (Eye & Ear Hospital)
melbourne.affiliation.departmentMelbourne Medical School
melbourne.affiliation.facultyAffiliate
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleCell Death Discovery
melbourne.source.volume4
melbourne.source.issue1
melbourne.identifier.arcFT140100047
melbourne.identifier.arcFT140100047
dc.rights.licenseCC BY
melbourne.elementsid1313990
melbourne.contributor.authorPebay, Alice
melbourne.contributor.authorWong, Ching-Bong
melbourne.contributor.authorLiu, Guei-Sheung
melbourne.contributor.authorLim, Shiang
melbourne.contributor.authorKong, Anne
melbourne.contributor.authorKemp, Bruce
melbourne.contributor.authorHernandez De Santiago, Hector
melbourne.contributor.authorWong, Ching Bong
melbourne.contributor.authorBond, Simon
dc.identifier.eissn2058-7716
melbourne.identifier.fundernameidAustralian Research Council, FT140100047
melbourne.identifier.fundernameidAustralian Research Council, FT140100047
melbourne.accessrightsOpen Access


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