CENTROSOME BIOGENESIS AND ADAPTIVE RESPONSE IN MAMMAL PARTHENOGENETIC CELLS

Human parthenotes have been proposed as a source of embryonic stem cells despite the high incidence of aneuploidy described in parthenotes of most mammalian species. Through a comparative analysis between parthenogenetic and bi-parental cells lines we found that parthenogenetic cells are affected by chromosomal instability and centrosome amplification. We provide evidence that both alterations are determined by the lack of paternal centriole, normally contributed by the sperm at the time of fertilization, but parthenogenetic cell lines activate a series of adaptive mechanisms that allow them to proliferate and differentiate. These include down-regulation of the p53/p21 pathway, massive increase of autophagic activity and formation of a wide network of intercellular bridges with the morphological and molecular characters of blocked cell abscissions. These processes are commonly observed in transformed cells therefore parthenogenesis may be used to explore the mechanisms regulating oncogenesis and their link with self-renewal and pluripotency in human cell lines.