The essentialome of the early differentiation and disease modeling using genome-wide screening in haploid human pluripotent stem cells

Diploidy (having two sets of chromosomes) is a fundamental genetic feature of essentially all cells of our body. An exception are the haploid germ cells, having only one set of chromosomes, resulting in a diploid genome upon fertilization. Human pluripotent stem cells are unique cells that can differentiate into all cell types in our body. We have recently established, for the first time, haploid human pluripotent stem cells stem cells. Using these extraordinary cells we were able to define, for the first time, the entire set of genes that are essential for human pluripotent stem cells, and regulate their unique features. We now propose to utilizing genetic screenings in haploid cells to identify the essentialome of the mature cells from the three embryonic germ layers. This analysis will give us a new perspective on early human embryogenesis and genetic disorders, and on our ability to differentiate the cells in order to use them in disease modeling and cell therapy.