Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4

Highlights•Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Esrrb, and Sall4 (7F) convert MEFs into iPSCs•RNA-seq and ATAC-seq reveal a distinct path for 7F reprogramming•7F cooperate to open and close chromatin during 7F reprogramming•7F activate a TF network to induce pluripotencySummaryReprogramming somatic cells to pluripotency by Oct4, Sox2, Klf4, and Myc represent a paradigm for cell fate determination. Here, we report a combination of Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb, and Sall4 (7F) that reprogram mouse embryonic fibroblasts or MEFs to chimera competent induced pluripotent stem cells (iPSCs) efficiently. RNA sequencing (RNA-seq) 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 establish an alternative paradigm for reprogramming that may be useful for analyzing cell fate control.Graphical abstract