University of California, Santa Barbara, United States
Abstract: Germline cells are responsible for passing genetic information from parent to offspring in sexually reproducing organisms. During mammalian embryonic development, molecular signals orchestrate the development of primordial germ cells (PGCs), the precursors to germline cells. As these PGCs mature, they undergo dramatic epigenetic remodeling, including genome-wide demethylation, that is central to their normal development towards gametes. Efforts to generate PGC-like cells (PGCLCs) in vitro from mouse pluripotent stem cells have been successful in replicating in vivo epigenetic remodeling, while human PGCLCs show more limited reprogramming, their dynamics are slower than in vivo, and the molecular signals necessary to induce the reprogramming are still unclear. To identify factors that trigger epigenetic remodeling in human PGCLC development, we conducted single-cell methylome and transcriptome sequencing on PGCLCs in extended culture for up to 21 days. From these results, we identified several candidate genes that were differentially expressed in PGCLCs with decreased methylation levels. Additional work is focused on validating candidate genes, DND1 and SOX15, as well as identifying additional candidate molecular epigenetic triggers. Gaining insight on mechanisms that govern epigenetic remodeling in PGCLCs will enable better in vitro models which are a valuable resource to study some forms of infertility.
