be230cLecture6

For the nascent ipsc addikonal barriers 3 need to be

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Unformatted text preview: 05934 Pluripotency Network Nanog Sox2,3 Oct4 Extra ­ embryonic ectoderm and mesoderm embryonic ectoderm BMP4 PrimiKve streak Mesoderm Endoderm Figure 1 The path from a somaKc cell to a refined iPSC and the putaKve epigeneKc barriers during the process. When reprogramming factors are introduced into a fibroblast, the reprogramming factors immediately drive the cell to overcome barrier 1, resulKng in the acquisiKon of the epithelial properKes through MET. A fibroblast that fails to conquer this barrier retains its cellular idenKty with either an accelerated or arrested proliferaKon status. Aaer the cell gains epithelial properKes, a subsequent barrier (2) to acquiring pluripotency is encountered. Intermediate epithelial cell that successfully overcomes the second barrier becomes a nascent iPSC, which can self ­renew independently of introduced transcripKon factors. Otherwise, it is trapped in the intermediate stage and becomes a parKally reprogrammed cell. For the nascent iPSC, addiKonal barrier(s) (3) need to be overcome acKvely or destructed passively to achieve a bona fide pluripotency equivalent to that in ESCs. Processes that depend on the reprogramming factors are shown in solid arrows, whose thickness reflects the approximate propensity for the cell to undergo a specific transiKon. Doged arrows represent the processes that require addiKonal manipulaKons other than the inducKon of reprogramming factors. PutaKve epigeneKc barriers in iPSC generaKon are numbered and shown in solid arcs. Other potenKal barriers are shown in doged arcs. 5 4/18/13 MODEL from Buganim et al. (Jaenisch), Cell 150: 1209 ­1222 (2012): A.  During iniKal 4 days, see inducKon of ~48 pluripotency and other genes. The order of inducKon is random, suggesKng a stochasKc process, e.g.the OSKM reprogramming factors iniKate probabalisKc events. This creates a meta ­stable state during which see expression of some lineage ­specific genes. Th...
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