Integrative Analysis of the Acquisition of Pluripotency in PGCs Reveals the Mutually Exclusive Roles of Blimp-1 and AKT Signaling

Stem Cell Reports. 2015 Jul 14;5(1):111-24. doi: 10.1016/j.stemcr.2015.05.007. Epub 2015 Jun 4.

Abstract

Primordial germ cells (PGCs) are lineage-restricted unipotent cells that can dedifferentiate into pluripotent embryonic germ cells (EGCs). Here we performed whole-transcriptome analysis during the conversion of PGCs into EGCs, a process by which cells acquire pluripotency. To examine the molecular mechanism underlying this conversion, we focused on Blimp-1 and Akt, which are involved in PGC specification and dedifferentiation, respectively. Blimp-1 overexpression in embryonic stem cells suppressed the expression of downstream targets of the pluripotency network. Conversely, Blimp-1 deletion in PGCs accelerated their dedifferentiation into pluripotent EGCs, illustrating that Blimp-1 is a pluripotency gatekeeper protein in PGCs. AKT signaling showed a synergistic effect with basic fibroblast growth factor plus 2i+A83 treatment on EGC formation. AKT played a major role in suppressing genes regulated by MBD3. From these results, we defined the distinct functions of Blimp-1 and Akt and provided mechanistic insights into the acquisition of pluripotency in PGCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Dedifferentiation / genetics*
  • Cell Lineage / genetics
  • Embryonic Germ Cells*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Germ Cells / cytology
  • Germ Cells / growth & development
  • Mice
  • Oncogene Protein v-akt / biosynthesis*
  • Oncogene Protein v-akt / genetics
  • Pluripotent Stem Cells*
  • Positive Regulatory Domain I-Binding Factor 1
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Prdm1 protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1
  • Oncogene Protein v-akt

Associated data

  • GEO/GSE67616