single-cell analysis: toward the clinic

 

human life starts with a single cell, the zygote, whichundergoes multiple mitotic cell divisions to form a completebody. during each cell division, the genome has tobe replicated to form the approximately 1014 cells thatmake up the adult human body. for a long time, it wasthought that all cells from the same individual harboredidentical genomes. th e only known exceptions beinglymphocytes, in which antigen- and pathogen-drivenrecom bination and hypermutation generate geneticdiversity, and germline cells, which undergo meiotic recombination.during normal mitotic cell division, however, the genome is not replicated with absolute precision; this results in the incorporation of somatic mutations. estimates that are based on known mutation rates suggest that every cell division creates some form of genetic variation, which may or may not have an effect on cellular function. during the progression from the zygotic stage to adulthood, these somatic mutations accumulate (figure 1). recent genome-wide assays have suggested that an individual does not have one genome, but is instead made up of a population of different cells. this situation is referred to as mosaicism, that is, the co-occurrence of several cell lineages with different genotypes in one individual who has developed from a single fertilized egg. the true extent of such mosaicism is unknown, but its presence appears to be the rule rather than the exception. estimates of the mutation burden in somatic cells are high and, as a consequence, it has been speculated that each cell in a human body may have a unique genomic signature; in other words, that each cell has its own ‘personal genome’.