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At early stage and late stage of cellular reprogramming the transgenes arouse two waves of transcription and epigenetic abruptly, while it is relatively quiet in intermediate stage. In this paper we analyzed the gene expression and chromatin modification data at different time point of mouse embryonic fibroblasts (MEFs) reprogramming at the single-cell resolution to assay how the cells progressing to reprogramming limit the transition rate after initiation phase. By comparing the gene expression profiling of refractory cells and progressing cells at day 3 and day 6 after factor induction, we observe over four times more differential expressed genes in refractory cells at this stage. These differentially expressed genes obtain more H3k27me3 to become bivalent, which resulting in aberrated downregulation of genes related to cell cycle, cell adhesion and development. Chromatin modifiers are found to be different regulated in these two cell populations. These observations reveal that the refractory cells responded the transcription signals earlier than the progressing cells and then fail to limit the transition rate in the intermediate phase. Differential stage- specific regulation of chromatin modifiers guide the cells into different way for reprogramming by controlling the raising of bivalent sites.

A Rate-limited Step Guided by Different Regulation of Chromatin Modifiers Should be Undergone after Initiation Phase in Cellular Reprogramming