Every cell in the body contains almost the same DNA, yet cells can become neurons, immune cells, cartilage-supporting cells, or many other specialized cell types. This thesis investigates how such cell fate decisions are controlled. It focuses on pluripotent stem cells, which can give rise to many cell types, and studies how their DNA is packaged, read, and protected while they change identity. The work maps dynamic chromatin networks across different stem cell states, reveals how the chromatin regulator ANKRD11 supports human neural development, and shows that early embryonic cells must silence part of their antiviral RNA-sensing system to avoid mistaking their own RNA for a viral infection. The thesis also translates these developmental principles into a regenerative strategy by generating stem-cell-derived macrophages that can reduce inflammation and protect cartilage in models of osteoarthritis. Together, the findings show how genome regulation guides development and how this knowledge may inspire new approaches for disease modelling and cell-based therapy.
Zicong Liu was born in 1995 in Neijiang, Sichuan, China. He obtained a master's degree in Biochemistry and Molecular Biology from Guangzhou Medical University and the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, in 2020. He then worked as a research assistant at the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, in 2020. In October 2021, he started his PhD research in Molecular Life Sciences at Radboud University under the supervision of Dr Hendrik Marks and Prof. Dr Michiel Vermeulen. His doctoral research focused on genome regulation, stem cell engineering, chromatin biology, neural development, innate immune regulation, and regenerative cell therapy.