Year 1

The development of novel experimental and computational approaches has made it possible to identify the spectrum of interacting genomic elements across the entire genome. Hence now it is feasible to assign specific enhancers to distinct promoters and to identify the ensemble of anchors associated with the folding pattern of the genome. During the past year we have identified the folding patterns of human embryonic stem cells to iPS cells derived from human B cells. Briefly, iPS cells derived from human B cells were generated as follows. Human B cells were isolated from human cord blood and transduced with viral vectors expressing Oct4, Sox2, KLF4 and c-Myc. From this population iPS cells were derived and expanded. Next the interactome of the iPS cells was determined and compared to that of human embryonic stem cells. Using an ensemble of computational strategies we found that the majority of genomic regions in iPS cells derived from human B cells was indistinguishable from that of human embryonic stem cells. However, we also found exceptions. Specifically, we found that approximately 700 genomic regions located throughout the genome showed differential nuclear positioning upon comparing iPS cells derived from human lymphoid cells to that of human embryonic stem cells. These data indicate that the majority of the genome derived from that of human embryonic stem cells shows a similar pattern in chromatin folding as compared to that of iPS cells derived from human B cells but that they differ from each other in a subset of genomic regions.