Project
Single-cell DNA and RNA sequencing of human cleavage and blastocyst stage embryos to study genomic instability and its functional impact on early development
The human genome is considered stable throughout development. However, recent analyses of human single cells –particularly of human preimplantation embryos following in vitro fertilization as well as of normal human primary tissue– challenge this dogma. Amazingly little is known about the true rate at which somatic DNA-mutation occurs, the different natures of the acquired mutations, as well as the cellular responses and selection processes that operate following genome mutation –particularly in early human embryogenesis. This project aims to apply a novel, state-of-the-art method for simultaneous genome and transcriptome sequencing (G&T-seq) of the same single cell to study the full spectrum of acquired DNA mutations in the embryo, the allocation of DNA variation to particular cell types during preimplantation human embryo development, as well as the impact of such acquired mutations on the transcriptional state or response of the cell. Last but not least, G&T-seq will reveal mechanistic insight in the DNA mutational processes operative during early human embryogenesis.