Polyploidy activates biological pathways related to morphogenesis in mammalian tissues

Abstract

Polyploid cells contain several copies of diploid genomes. These cells were found in all mammalian tissues where they were searched. In physiological conditions, genome accumulation is a part of development and differentiation programs. Polyploid cells present in heart, skin epithelium, placenta, liver, brain, and blood.1 In stressful condition polyploidy accompanies and stimulates pathological processes. Thus, the increase of polyploidy was documented in hypertensive heart, atherosclerotic vessels, cirrhotic liver and cancer.2 Despite ubiquitous distribution, the effect of polyploidy on gene expression remains not completely understood. Increasing evidence suggests that cell polyploidy may epigenetically alter gene expression and miRNA gene transcription in plants as well as in animals.3,4 miRNA which are short (20-22 nucleotide long) noncoding RNA reported to play various roles in human, plant and in some viruses.5,6 The impact of polyploidy on the transcriptome was investigated in hepatocytes, megakaryocytes, vascular epithelial cells, and placenta. Investigation of the differences in expression using the conservative double threshold led investigators to the conclusion that among several thousand genes not a single one is affected by polyploidy (as in the case of hepatocytes) or only several dozen genes are reactive.7 Moreover, for each cell type, this small set of genes turned out to be different. For instance, in the cells of vascular epithelium, several genes associated with the immune system were suppressed;8 in megakaryocytes, activation of tissue specific genes was registered; and, in decidual cells, activation of nuclear genes encoding mitochondrial proteins was detected.9 These differences suggest that the full effect of somatic polyploidy (if it exists) has not been identified yet. The absence of consensus is not surprising because mmaintaining gene dosage balance, polyploidy has little impact on separate gene activity. The weakness of ploidy associated effects make it difficult to identify common gene expression signature. At the same time, modifying activity of thousands of genes at a time, polyploidy participates in coordination of postnatal development, developmental programming, differentiation and pathogenesis of many diseases, including cardiovascular diseases and cancer.2,7,10–12