Organ-specific barcodes in human fetal development and stem cell differentiation : the pancreas in the spotlight

Roost, M.S. (2017)

Doctoral Thesis

In chapter 2, the pancreas was used as a paradigm to study human organ development and assess the quality of our fetal material. In a descriptive, histochemical study, we investigated how blood and lymphatic vascular networks develop and their association with basement membranes and smooth muscle cells between gestational weeks 9 and 22 (W9 and W22).
In Chapter 3, 4 and 5, we analyzed a total of 21 fetal organs and maternal endometrium at three time points (W9, W18 and W22) at the transcriptional and epigenetic level, thereby, providing an atlas of human organ development.
The rare fetal material also allowed us to investigate the presence of an epigenetic memory from the cell of origin in induced pluripotent stem cells (iPSCs). We generated isogenic iPSC lines from six fetal organs (brain, skin, kidney, muscle, lung and pancreas) in chapter 5. The six iPSC lines had very similar DNA methylation profiles, however, we showed that the two clones derived from the brain harbored 18 hypermethylated and 6 hypomethylated CpGs also found in the fetal brain and we demonstrated that the brain-iPSC clones appeared to have a differentiation bias towards neural derivatives when comparing neural differentiation of the brain- and skin-iPSC clones.

• Stem Cells
• Pancreas
• Human Fetal Development
• Epigenetic Memory
• Transcriptomics
• Epigenetics

• All authors: Roost, M.S.
• Supervisor: Mummery, C.L.; Koning, E.J.P. de
• Co-supervisor: Chuva de Sousa Lopes, S.M.
• Committee: Hogendoorn, P.C.W.; Goeman, J.J.; Slagboom, P.; Sonnenberg, A.; Hanley, N.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2017-03-22
• ISBN (print): 9783033060791
• Sponsorship: Bontius Stichting Netherlands Organisation for Scientific Research Interuniversity Attraction Poles