Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation

Jessica Rosati, Francesco Spallotta, Simona Nanni, Annalisa Grasselli, Annalisa Antonini, Sara Vincenti, Carlo Presutti, Claudia Colussi, Carmen D'Angelo, Anna Biroccio, Antonella Farsetti, Maurizio C. Capogrossi, Barbara Illi, Carlo Gaetano

Research output: Contribution to journalArticle

Abstract

Objective- Smad-interacting protein-1 (Sip1/ZEB2) is a transcriptional repressor of the telomerase reverse transcriptase catalytic subunit (Tert) and has recently been identified as a key regulator of embryonic cell fate with a phenotypic effect similar, in our opinion, to that reported for nitric oxide (NO). Remarkably, SIP1/ZEB2 is a known target of the microRNA 200 (miR-200) family. In this light, we postulated that Sip1/ZEB2 and the miR-200 family could play a role during the NO-dependent differentiation of mES. Methods and Results- The results of the present study show that Sip1/ZEB2 expression is downregulated during the NO-dependent expression of mesendoderm and early cardiovascular precursor markers, including Flk1 and CXCR4 in mES. Coincidently, members of the miR-200 family, namely miR-429, -200a, -200b, and -200c, were transcriptionally induced in parallel to mouse Tert. This regulation occurred at the level of chromatin. Remarkably, miR-429/miR-200a overexpression or Sip1/ZEB2 knockdown by short hairpin RNA interference elicited a gene expression pattern similar to that of NO regardless of the presence of leukemia inhibitory factor. Conclusion- These results are the first demonstrating that the miR-200 family and Sip1/ZEB2 transcription factor are regulated by NO, indicating an unprecedented molecular circuitry important for telomerase regulation and early differentiation of mES.

Original languageEnglish
Pages (from-to)898-907
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • biology developmental
  • differentiation
  • epigenetics
  • gene expression
  • microRNA
  • molecular biology
  • nitric oxide
  • vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Rosati, J., Spallotta, F., Nanni, S., Grasselli, A., Antonini, A., Vincenti, S., Presutti, C., Colussi, C., D'Angelo, C., Biroccio, A., Farsetti, A., Capogrossi, M. C., Illi, B., & Gaetano, C. (2011). Smad-interacting protein-1 and microRNA 200 family define a nitric oxide-dependent molecular circuitry involved in embryonic stem cell mesendoderm differentiation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(4), 898-907. https://doi.org/10.1161/ATVBAHA.110.214478