Unbalanced development and progressive repair in human early mosaic and chimeric embryos

Abstract

With the advancement of genetics and genetic diagnosis, more and more human mosaics and chimeras and even unprecedented type of them have been identified. Especially in the era of universal prenatal screening, human mosaics and chimeras have often been revealed in the embryonic and fetal period with high accuracy. Although mosaicism and chimerism are abnormal in theory, some of them have no detectable effect on embryonic, fetal and postnatal growth and development and adulthood life, which increases difficulties being assessed during genetic counseling. In addition, the following intriguing observations on human mosaicism and chimerism are frequently reported. Continuous prenatal diagnoses indicate that the degree of fetal mosaicism is reduced in some subjects; Mosaicism and chimerism distribute differentially among tissues and organs of an individual; Cells with chromosomal abnormality gradually decrease or even disappear after birth, and are eventually replaced by normal cells. However, to our knowledge, we do not understand how these mosaicisaic and chimerisic phenomenon occur. Here, we propose a hypothesis of unbalanced development and progressive repair to elucidate the underlying mechanisms of these unique mosaic and chimeric phenomenon. The hypothesis is that unbalanced development and progressive repair of human mosaicism and chimerism are achieved by selective pressure and genetic control during development, clonal depletion associated with distinct apoptosis or differentiation potential and heterogoneic division and biased allocation. If this hypothesis is proven, these proposed mechanisms are of great clinical significance in the diagnosis and management of embryonic and fetal mosaicism or chimerism.