Gametes are cells that have the unique ability to give rise to new individuals as well as transmit (epi)genetic information across generations. Generation of functionally competent gametes, oocytes... Show moreGametes are cells that have the unique ability to give rise to new individuals as well as transmit (epi)genetic information across generations. Generation of functionally competent gametes, oocytes and sperm cells, depends to some extent on several fundamental processes that occur during fetal development. Direct studies on human fetal germ cells remain hindered by ethical considerations and inaccessibility to human fetal material. Therefore, the majority of our current knowledge of germ cell development still comes from an invaluable body of research performed using different mammalian species. During the last decade, our understanding of human fetal germ cells has increased due to the successful use of human pluripotent stem cells to model aspects of human early gametogenesis and advancements on single-cell omics. Together, this has contributed to determine the cell types and associated molecular signatures in the developing human gonads. In this review, we will put in perspective the knowledge obtained from several mammalian models (mouse, monkey, pig). Moreover, we will discuss the main events during human fetal (female) early gametogenesis and how the dysregulation of this highly complex and lengthy process can link to infertility later in life. Show less
Zinc-Finger (ZnF) proteins represent one of the most abundant group of proteins in the human genome. At first characterized as DNA binding proteins, it has become increasingly clear that ZnF... Show moreZinc-Finger (ZnF) proteins represent one of the most abundant group of proteins in the human genome. At first characterized as DNA binding proteins, it has become increasingly clear that ZnF-proteins have the ability to bind a large variety of substrates such as RNAs, proteins and post-translational modifications, suggesting potential roles in a variety of biological processes. Indeed, several studies have implicated ZnF-proteins for instance in transcription regulation, signal transduction and cell migration. Intriguingly, more recently these proteins have emerged as important protectors of the genome, particularly by orchestrating the repair of highly deleterious DNA double-strand breaks. Here we provide a comprehensive summary of the roles of ZnF domain-containing proteins in DNA double-strand break repair and discuss how their dysfunction impacts genome stability and human disease. Show less
