Accessing Pluripotency from the Somatic Side

We report that Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F) convert MEFs to chimera competent iPSCs with fast kinetics. Time lapse microscopy reveal morphological changes distinct for 7F and Yamanaka factor (YF) reprogramming. Bulk transcriptomic analyses suggest that 7F and YF share 927 up and 548 down regulated genes, but differ in 1138 YF and 427 7F specifically activated genes. Single cell RNA sequencing reveals a fate path that can be further resolved into a cell fate continuum based on a MEF/ESC scoring system. A crossing point marks the transition in the continuum from somatic to pluripotent fates. By sampling the leading cells along this continuum, we identified transition stages marked by novel nu-clear factors and cell surface molecules. Our results reveal an efficient path to pluripotency and suggest that cell fate is governed by intrinsic fac-tors accessible by diverse approaches To explore the dynamics process of the 7F reprogramming system, we isolated singel cells at D0, D1, D3, D4, D5, D7 using Fluidigm C1 system, totally we got 461 high quality single cells data sets.