Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression

Koji Nishihara, Takahiro Shiga, Eri Nakamura, Tomohiko Akiyama, Takashi Sasaki, Sadafumi Suzuki, Minoru Ko, Norihiro Tada, Hideyuki Okano, Wado Akamatsu

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2 Citations (Scopus)


Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3β (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state.

Original languageEnglish
Pages (from-to)305-318
Number of pages14
JournalStem Cell Reports
Issue number2
Publication statusPublished - 2019 Feb 12



  • 2-cell genes
  • 3i
  • culture conditions
  • differentiation potentials
  • induced pluripotent stem cells (iPSCs)
  • Zscan4

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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