Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/39677

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Hartogh, S.C. den (2016)

Fluorescent gene reporters in human pluripotent stem cells : as model for studying human heart development and cardiomyocyte differentiation

Doctoral Thesis
It is critical to gain knowledge in the underlying mechanisms that control human cardiovascular developm ent, which helps us to understand the onset of congenital cardiovascular diseases, and to develop optimal culture methods for efficient in vitro cardiomyocyte differentiation from hPSCs, which are of interest for final translational applications including screening and efficacy assays for disease modelling, drug discovery and development, personalized medicine, and perhaps the regeneration of cardiovascular tissues for therapeutic purposes. In this thesis, we show how genetic manipulation of human pluripotent stem cells (hPSCs), resulting in the genomic integration of a fluorescent protein encoding sequence at the locus of a key cardiac transcription factor, allows us to visualize and isolate early pre-cardiac progenitors subpopulations, and to study the molecular mechanisms involved in their further differentiation to cells of the cardiac lineage, including smooth muscle...Show more It is critical to gain knowledge in the underlying mechanisms that control human cardiovascular developm ent, which helps us to understand the onset of congenital cardiovascular diseases, and to develop optimal culture methods for efficient in vitro cardiomyocyte differentiation from hPSCs, which are of interest for final translational applications including screening and efficacy assays for disease modelling, drug discovery and development, personalized medicine, and perhaps the regeneration of cardiovascular tissues for therapeutic purposes. In this thesis, we show how genetic manipulation of human pluripotent stem cells (hPSCs), resulting in the genomic integration of a fluorescent protein encoding sequence at the locus of a key cardiac transcription factor, allows us to visualize and isolate early pre-cardiac progenitors subpopulations, and to study the molecular mechanisms involved in their further differentiation to cells of the cardiac lineage, including smooth muscle cells, endothelial cells, and cardiomyocyte subtypes.Show less
Stem Cells
Cardiomyocytes
Human, Pluripotent
Fluorescent reporter
Differentiation
Cell Culture
All authors
Hartogh, S.C. den
Supervisor
Mummery, C.L.; Passier, R.
Committee
Laake, L. van; Zweigerdt, R.; Staal, F.; Goumans, M.J.; Rooij, E. van
Qualification
Doctor (dr.)
Awarding Institution
Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2016-05-18
ISBN (print)
9789462954823

Funding

Sponsorship
Rembrandt Institute for Cardiovascular Research Nederlandse Hartstichting Stichting Proefdiervrij