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Abstrakt
BAF Complex Enhances Reprogramming of Adult Human Fibroblasts
Nishant Singhal, Marcos J. Arauzo-Bravo, Martina Sinn and Holm Zaehres
Chromatin remodeling molecules of the BAF complex, Brg1 and Baf155, as well as other chromatin remodeling molecules have been described to enhance Oct4, Sox2, Klf4 and c-Myc mediated reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs). Brg1 maintains pluripotency of mouse embryonic stem cells (mESCs) by modulating the expression of pluripotent genes including Oct4 in synergy with LIF/STAT signaling. While mESCs depend on LIF/STAT signaling, human embryonic stem cells (hESCs) use bFGF signaling to maintain pluripotency. Interestingly, unlike mESCs, BAF complex in hESCs is composed of both BAF155 and BAF170, where BAF170 plays a role in maintaining hESCs pluripotency. In this study we describe how BRG1 and BAF155 enhance reprogramming of adult human fibroblasts. Overexpression of BAF155 does not affect pluripotency of hiPSCs as tested by global gene expression profiling as well as in vivo and in vitro assays. Additionally, these findings show that BRG1 and BAF155 expression can enhance reprogramming even in the absence of LIF/STAT signaling.