title: Human Germline: A New Research Frontier.
abstract: We recently elucidated the mechanism of human primordial germ cell (hPGC) specification and resetting of the epigenome for totipotency. The regulators of hPGC specification also initiate resetting of the epigenome, leading to a comprehensive erasure of DNA methylation, erasure of imprints and X reactivation in early hPGCs in vivo. These studies reveal differences with the mouse model, which are probably due to differences in the regulation of human pluripotency, and in postimplantation development at gastrulation, which indicates the importance of non-rodent models for investigations. Within the extreme hypomethylated environment of the early human germline are loci that are resistant to DNA demethylation, with subsequent predominant expression in neural cells. These loci provide a model for studies on the mechanism of transgenerational epigenetic inheritance, and their response to environmental factors. Such epigenetic mechanism of inheritance could potentially provide greater phenotypic plasticity, with significant consequences for human development and disease.
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 3EG, UK. Electronic address: a.surani@gurdon.cam.ac.uk.
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins