Understanding the Role of ZNF765 and/or L1PA Retroelements in Defining Embryonic Stem Cell Phenotypes
Engineering
Biomolecular Engineering: Senior Thesis Research
Many regulatory mechanisms during early development remain largely unexplored in humans. These mechanisms vary throughout species and by better understanding what these mechanisms are, we can gain a better grasp on how malfunctions in those mechanisms result in early developmental diseases in humans. To begin to delve into this issue, it is important to learn which genetic components serve a role in regulating those mechanisms. I believe that ZNF765 and/or the retroelements that are regulated by ZNF765 are such components that play an important developmental role. I want to show that they help define naive or primed embryonic stem phenotypes. I plan to generate datasets of the transcriptomes of prime and naive cells in the presence and absence of ZNF765 to see if naive-associated genes, prime-associated genes, or retroelements are up-regulated or down-regulated when the expression of ZNF765 is altered. To accomplish this, I have shown that I can create conditions were ZNF765 expression is greatly reduced through CRISPRi in prime stem cells. I have also verified that I can activate naive-associated genes through a naive conversion using feeder-free media. These findings will allow me or other Haussler lab members to verify the same conditions in naive cells to generate transcriptome datasets that will let us determine whether ZNF765 and or the retroelements regulated by it play an early developmental regulatory role in prime and naive cells.
