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

Cell Rep. 2019 Jun 18;27(12):3473-3485.e5. doi: 10.1016/j.celrep.2019.05.068.

Abstract

Reprogramming 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Cellular Reprogramming / genetics*
  • Chimera / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Euchromatin / genetics
  • Euchromatin / metabolism
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Kruppel-Like Factor 4
  • MAP Kinase Kinase 6 / genetics
  • MAP Kinase Kinase 6 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism*
  • RNA-Seq
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Euchromatin
  • F-Box Proteins
  • Glis1 protein, mouse
  • Heterochromatin
  • Jundp2 protein, mouse
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Repressor Proteins
  • Sall4 protein, mouse
  • Transcription Factors
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm2b protein, mouse
  • MAP Kinase Kinase 6
  • Map2k6 protein, mouse