The E1a Adenoviral Gene Upregulates the Yamanaka Factors to Induce Partial Cellular Reprogramming

Cells. 2023 May 7;12(9):1338. doi: 10.3390/cells12091338.

Abstract

The induction of pluripotency by enforced expression of different sets of genes in somatic cells has been achieved with reprogramming technologies first described by Yamanaka's group. Methodologies for generating induced pluripotent stem cells are as varied as the combinations of genes used. It has previously been reported that the adenoviral E1a gene can induce the expression of two of the Yamanaka factors (c-Myc and Oct-4) and epigenetic changes. Here, we demonstrate that the E1a-12S over-expression is sufficient to induce pluripotent-like characteristics closely to epiblast stem cells in mouse embryonic fibroblasts through the activation of the pluripotency gene regulatory network. These findings provide not only empirical evidence that the expression of one single factor is sufficient for partial reprogramming but also a potential mechanistic explanation for how viral infection could lead to neoplasia if they are surrounded by the appropriate environment or the right medium, as happens with the tumorogenic niche.

Keywords: E1a gene; Yamanaka factors; adenovirus; embryonic stem cells; induced pluripotent stem cells; reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cellular Reprogramming* / genetics
  • Fibroblasts / metabolism
  • Induced Pluripotent Stem Cells* / metabolism
  • Kruppel-Like Factor 4
  • Mice

Substances

  • Kruppel-Like Factor 4

Grants and funding

This research was supported by Instituto de Salud Carlos III (ISCIII) (PI19/01007 and DTS21/00130) and by Fondo Europeo de Desarrollo Regional (Feder) “Una manera de hacer Europa”. We also thank CIBER-BBN, an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III (ISCIII) with the assistance of the European Regional Development Fund. This study was also partially funded by the Aragon Government (Ph.D. Grant No.r B054/12) and cofounded by Aragon/FEDER 2014–2020 “Building Europe from Aragon”. GM gratefully acknowledges the support from the Miguel Servet Program (MS19/00092; ISCIII).