Non-Random Chromosome Segregation in Stem Cells

There are many small bits of conventional wisdom in biology whose general truths may be widely assumed, despite limited evidence from rather narrow circumstances. One such bit of wisdom concerns the random separation of chromosomes into daughter cells during mitosis. In a new study, Thomas Rando and colleagues show that for muscle stem cells, that separation is anything but random. Before every mitotic cell division, each chromosome must be copied in full to ensure that each daughter cell has a complete complement of genes as it begins its new life. During replication, the double helix is pulled apart, and each strand serves as the template for creating a new opposite strand. After replication, the two copies, called sister chromatids, are each half old and half brand new (hence the name " semi-conservative " replication). During mitosis, these chromatid pairs are separated from each other, one pulled into one nascent daughter cell, the other pulled into the other. If we were to paint both old strands white and both new strands green, say, and watch one complete cycle of replication and mitosis, we would fi rst see the two original white strands pulled apart, then make new green partners, and fi nally be pulled into daughter cells, one green-white pair going one way, the other going the other. Each human cell contains 46 chromosomes, and during mitosis, each daughter cell receives 46 chromatids (which are rechristened as chromosomes as soon as they separate from their sister). If we were to paint all 92 old strands white and 92 new strands green and watch them during the fi rst round of cell division, we'd fi rst see 92 older white strands get pulled apart, then they would make 92 green partners, and then we would see 92 green-white pairs get pulled into daughter cells, 46 going one way, 46 going the other. But if we went on to watch one of these cells go through the next round, it would not be so easy to predict what would happen to our white strands. We begin this round with only 46 older white strands, one in each chromosome, and after replication, each four-stranded chromatid pair would contain only one white strand. During mitosis, each chromatid pair is separated, and 46 white strands would get pulled into daughter cells. But what determines how these 46 are distributed? Is it random? Half to each daughter? …