Upregulation of the Yamanaka's factors by single adenoviral gene cellular reprogramming
G Mendoza(1) R González-Pastor(2) J M Sánchez(3) A Arce-Cerezo(4) M Quintanilla(5) G Moreno-Bueno(6) A de Martino(2) E Riu(4) T Rodriguez(3) P Martin-Duque(1,2,7,8)
1:IIS Aragón; 2:Instituto Aragonés de Ciencias de la Salud; 3:Imperial College London; 4:Universidad Autónoma de Barcelona (UAB); 5:IIB Alberto Sols; 6:Universidad Autònoma de Madrid; 7:Fundación Araid; 8:Universidad de Zaragoza
The induction of pluripotency by enforced expression of different sets of genes in somatic cells has been achieved with reprogramming technologies firstly described by the 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 expression of two of the Yamanaka factors (c-Myc and Oct-4) as well as epigenetic changes.
Here, we demonstrate that 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 empirical evidence that expression of one single factor is sufficient for reprogramming to the epiblast stage.
ACKNOWLEDGEMENTS: This research was supported by Instituto de Salud Carlos III (ISCIII) (PI19/01007 and DTS21/00130). We also thank CIBER‐BBN financed by the Instituto de Salud Carlos III (ISCIII) with the assistance of the European Regional Development Fund.
The authors thank the Scientific and Technical Services at CIBA (IACS), especially tissue culture, microscopy, imaging, flow cytometry and pathology.