Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/136521

In Collections

This item can be found in the following collections:

Cao, X. (2020)

Modeling vascular diseases using human induced pluripotent stem cells

Doctoral Thesis
Abnormal vascular physiology and precipitating inflammatory pathways underlie many different diseases, including hemorrhage, stroke, vascular dementia and even cancer. Pluripotent stem cells (PSCs) can now be derived by reprogramming from any individual so that it is possible in principle to derive all somatic cells of the human body that would normally be difficult to access. In this thesis, I studied the derivation of myeloid cells from human induced pluripotent stem cells (hiPSCs) to model the inflammatory component of vascular disease and characterized the development path of hiPSC-derived endothelial cells (hiPSC-ECs) which form the vascular walls. Functional defects in either of these cell types can cause or exacerbate vascular disease. I then used these cell types to gain insight into the mechanisms underlying two genetic diseases: Hereditary Hemorrhagic Telangiectasia (HHT) which is caused by mutations in a gene called Endoglin expressed on cells of...Show moreAbnormal vascular physiology and precipitating inflammatory pathways underlie many different diseases, including hemorrhage, stroke, vascular dementia and even cancer. Pluripotent stem cells (PSCs) can now be derived by reprogramming from any individual so that it is possible in principle to derive all somatic cells of the human body that would normally be difficult to access. In this thesis, I studied the derivation of myeloid cells from human induced pluripotent stem cells (hiPSCs) to model the inflammatory component of vascular disease and characterized the development path of hiPSC-derived endothelial cells (hiPSC-ECs) which form the vascular walls. Functional defects in either of these cell types can cause or exacerbate vascular disease. I then used these cell types to gain insight into the mechanisms underlying two genetic diseases: Hereditary Hemorrhagic Telangiectasia (HHT) which is caused by mutations in a gene called Endoglin expressed on cells of the vascular wall and inflammatory macrophages, and a vascular tumor called Pseudomyogenic hemangioendothelioma (PHE) in which endothelial cells are thought to be the tumor cell of origin. I developed new differentiation protocols to generate inflammatory cells from hiPSC, characterized these cells functionally and used Next-Generation Sequencing and bioinformatic analysis to gain insight into the molecular pathways controlling development of one particular type of endothelial cells from hiPSC and the underlying tumorigenic mechanisms of PHE.Show less
Endothelial cells
Myeloid cells
Macrophages
Hereditary Hemorrhagic Telangiectasia (HHT)
Pseudomyogenic hemangioendothelioma (PHE)
single cell RNA sequencing
Organoid
Blood vessel
Monocytes
All authors
Cao, X.
Supervisor
Mummery, C.L.
Co-supervisor
Orlova, V.V.
Committee
Goumans, M.J.T.H.; Passier, P.C.J.J.; Semrau, S.; Staal, F.J.T.; Salvatori, D.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2020-09-09
ISBN (print)
9789492597434