Single-cell transcriptional atlas of Giardia encystation

Project Summary Differentiation into dormant encapsulated cell types, known as encystation, is one of the most common modes of eukaryotic differentiation. Importantly, these changes cause the parasites to release from the host intestine, thus this process could be targeted to clear infections and/or block transmission. Despite its importance, very little is understood about the regulation of Giardia encystation. Here we propose to use single-cell RNA sequencing (scRNAseq) to build an atlas of gene expression during the cell cycle (Aim1) and during differentiation into cysts (Aim2). cAMP signaling is necessary and sufficient to initiate the encystation but not induce the formation of fully formed cysts. Hence, additional signals are required for cyst formation, and we aim to address this important question using scRNAseq. Together these studies will deepen our understanding of the encystation program and reveal unappreciated pathways that work to control the balance between persistence of infection versus transmission of this major parasite and model for the regulation of encystation.