Chromosome-specific non-random sister chromatid segregation during stem cell division

Adult stem cells undergo asymmetric cell division to self-renew and give rise to differentiated cells that comprise mature tissue(1). Sister chromatids may be distinguished and segregated non-randomly in asymmetrically dividing stem cells(2), although the underlying mechanism and the purpose it may serve remain elusive. We developed the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique(3) with single-chromosome resolution and show that sister chromatids of X and Y chromosomes, but not autosomes, are segregated non-randomly during asymmetric divisions of Drosophila male germline stem cells (GSCs). This provides the first direct evidence that two sister chromatids containing identical genetic information can be distinguished and segregated non-randomly during asymmetric stem cell divisions. We further show that the centrosome, SUN-KASH nuclear envelope proteins, and Dnmt2 are required for non-random sister chromatid segregation. Our data suggest that the information on X and Y chromosomes that enables non-random segregation is primed during gametogenesis in the parents. Moreover, we show that sister chromatid segregation is randomized in GSC overproliferation and dedifferentiated GSCs. We propose that non-random sister chromatid segregation may serve to transmit distinct information carried on two sister chromatids to the daughters of asymmetrically dividing stem cells.