Induction of Pluripotency by Alternative Factors

Reprogramming somatic cells to pluripotency represents a paradigm for cell fate determination. A binary logic of closing and opening chromatin provides a simple way to understand iPSC reprogramming driven by both Yamanaka factors or chemicals. Here we apply this logic to design a combination of Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F) that reprogram MEFs to chimera competent iPSCs efficiently. RNA- and ATAC-seq reveal distinct mechanisms for 7F induction of pluripotency. Dropout experiments further reveal a highly cooperative process among 7F to dynamically close and open chromatin loci that encode a network of transcription factors to mediate reprogramming. These results reveal a previously unknown path between somatic and pluripotent states and open new doors for cell fate control.