ZSCAN4+ mouse embryonic stem cells have an oxidative and flexible metabolic profile

Annaelena Troiano, Consiglia Pacelli, Vitalba Ruggieri, Rosella Scrima, Martina Addeo, Francesca Agriesti, Valeria Lucci, Gina Cavaliere, Maria Pina Mollica, Marianna Caterino, Margherita Ruoppolo, Simona Paladino, Daniela Sarnataro, Feliciano Visconte, Francesco Tucci, Piervito Lopriore, Viola Calabrò, Nazzareno Capitanio, Claudia Piccoli, Geppino Falco

Research output: Contribution to journalArticlepeer-review


Cultured mouse embryonic stem cells are a heterogeneous population with diverse differentiation potential. In particular, the subpopulation marked by Zscan4 expression has high stem cell potency and shares with 2 cell stage preimplantation embryos both genetic and epigenetic mechanisms that orchestrate zygotic genome activation. Although embryonic de novo genome activation is known to rely on metabolites, a more extensive metabolic characterization is missing. Here we analyze the Zscan4+ mouse stem cell metabolic phenotype associated with pluripotency maintenance and cell reprogramming. We show that Zscan4+ cells have an oxidative and adaptable metabolism, which, on one hand, fuels a high bioenergetic demand and, on the other hand, provides intermediate metabolites for epigenetic reprogramming. Our findings enhance our understanding of the metastable Zscan4+ stem cell state with potential applications in regenerative medicine.

Original languageEnglish
Article numbere48942
JournalEMBO Reports
Issue number6
Publication statusPublished - Jun 4 2020


  • cell intermediate metastate
  • embryonic stem cells
  • heterogeneity
  • metabolism
  • pluripotency

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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