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postgraduate thesis: Combinatorial expression of critical Ca²⁺ handling proteins in human embryonic stem cell-derived cardiomyocytes

TitleCombinatorial expression of critical Ca²⁺ handling proteins in human embryonic stem cell-derived cardiomyocytes
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Li, L. [李力]. (2015). Combinatorial expression of critical Ca²⁺ handling proteins in human embryonic stem cell-derived cardiomyocytes. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5699954
AbstractThe self-renewable human embryonic stem cells (hESCs) represent a potential unlimited ex vivo source of human cardiomyocytes that could be used for applications in disease modeling, cardiotoxicity screening, drug discovery, and cell-based therapies. The rise and decay of 〖Ca〗^(2+) during the excitation–contraction process is known as the 〖Ca〗^(2+) transient and a precise modulation of such transient plays an important part of the cardiomyocytes contractility. An array of 〖Ca〗^(2+)-handling proteins is responsible for the regulation of the 〖Ca〗^(2+) transient. Many of these proteins, are, however, sub-optimally expressed or even absent in hESC-CMs, comparing to normal adult CMs. Previous efforts made on the individual overexpression of 〖Ca〗^(2+)-handling proteins like Calsequestrin (CSQ), Phospholamban (PLB) and Sarcoplasmic Reticulum Calcium ATPase 2a (SERCA2a) showed positive maturation of 〖Ca〗^(2+) handling, but the effect of combinatorial overexpression of multiple 〖Ca〗^(2+)-handling proteins simultaneously in hESC-CMs have never been examined. In this work, I have taken a lentiviral-based transgenes delivery approach to try to simultaneously overexpress 3 critical 〖Ca〗^(2+) handling proteins (CSQ, PLB, SERCA2a) that are insufficiently expressed in hESC-CMs and subsequently examined the functional consequences following successful combinatorial overexpression. My results indicate that overexpressing 〖Ca〗^(2+) handling proteins can definitely cause to consequential phenotypic changes regarding the 〖Ca〗^(2+) handling of hESC-CMs but a carefully titration for an optimal combination of different proteins will be needed in order to fulfill an overall driven maturation of the 〖Ca〗^(2+) handling of hESC-CMs.
DegreeMaster of Philosophy
SubjectEmbryonic stem cells
Heart cells
Calcium - Physiological effect
Dept/ProgramBiomedical Sciences
Persistent Identifierhttp://hdl.handle.net/10722/223049

 

DC FieldValueLanguage
dc.contributor.authorLi, Li-
dc.contributor.author李力-
dc.date.accessioned2016-02-17T23:14:40Z-
dc.date.available2016-02-17T23:14:40Z-
dc.date.issued2015-
dc.identifier.citationLi, L. [李力]. (2015). Combinatorial expression of critical Ca²⁺ handling proteins in human embryonic stem cell-derived cardiomyocytes. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5699954-
dc.identifier.urihttp://hdl.handle.net/10722/223049-
dc.description.abstractThe self-renewable human embryonic stem cells (hESCs) represent a potential unlimited ex vivo source of human cardiomyocytes that could be used for applications in disease modeling, cardiotoxicity screening, drug discovery, and cell-based therapies. The rise and decay of 〖Ca〗^(2+) during the excitation–contraction process is known as the 〖Ca〗^(2+) transient and a precise modulation of such transient plays an important part of the cardiomyocytes contractility. An array of 〖Ca〗^(2+)-handling proteins is responsible for the regulation of the 〖Ca〗^(2+) transient. Many of these proteins, are, however, sub-optimally expressed or even absent in hESC-CMs, comparing to normal adult CMs. Previous efforts made on the individual overexpression of 〖Ca〗^(2+)-handling proteins like Calsequestrin (CSQ), Phospholamban (PLB) and Sarcoplasmic Reticulum Calcium ATPase 2a (SERCA2a) showed positive maturation of 〖Ca〗^(2+) handling, but the effect of combinatorial overexpression of multiple 〖Ca〗^(2+)-handling proteins simultaneously in hESC-CMs have never been examined. In this work, I have taken a lentiviral-based transgenes delivery approach to try to simultaneously overexpress 3 critical 〖Ca〗^(2+) handling proteins (CSQ, PLB, SERCA2a) that are insufficiently expressed in hESC-CMs and subsequently examined the functional consequences following successful combinatorial overexpression. My results indicate that overexpressing 〖Ca〗^(2+) handling proteins can definitely cause to consequential phenotypic changes regarding the 〖Ca〗^(2+) handling of hESC-CMs but a carefully titration for an optimal combination of different proteins will be needed in order to fulfill an overall driven maturation of the 〖Ca〗^(2+) handling of hESC-CMs.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshEmbryonic stem cells-
dc.subject.lcshHeart cells-
dc.subject.lcshCalcium - Physiological effect-
dc.titleCombinatorial expression of critical Ca²⁺ handling proteins in human embryonic stem cell-derived cardiomyocytes-
dc.typePG_Thesis-
dc.identifier.hkulb5699954-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineBiomedical Sciences-
dc.description.naturepublished_or_final_version-

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