Since the initial discovery that OCT4, SOX2, KLF4, and c-MYC overexpression sufficed for the induction of pluripotency in somatic cells, methodologies replacing the original factors have enhanced our understanding of the reprogramming process. However, unlike in mouse, OCT4 has not been replaced successfully during reprogramming of human cells. Here we report on a strategy to accomplish this replacement. Through a combination of transcriptome and bioinformatic analysis we have identified factors previously characterized as being lineage specifiers that are able to replace OCT4 and SOX2 in the reprogramming of human fibroblasts. Our results show that it is possible to replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the reprogramming of human cells. At a broader level, they also support a model in which counteracting lineage specification networks underlies the induction of pluripotency.
|Original language||English (US)|
|Number of pages||10|
|Journal||Cell Stem Cell|
|State||Published - Sep 5 2013|
Bibliographical noteFunding Information:
We thank M. Schwarz for administrative support. We also thank Montserrat Barragan, Lola Mulero, Cristina Morera, Rafaella Fazzina, Kelly Herbert, and Krystal Moon for expert technical assistance and Lara Nonell and Eulalia Puigdecanet at the Microarray Service (SAM) of IMIM-Hospital del Mar for microarray processing and analysis. I.S.M. was partially supported by a Nomis Foundation postdoctoral fellowship. E.N. was partially supported by a F.M. Kirby Foundation postdoctoral fellowship. Work in the laboratory of J.C.I.B. was supported by grants from Fundacion Cellex, the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust and Ministerio de Economia y Competitividad (MINECO), CIBER-BBN, TERCEL-ISCIII- MINECO, and Cardiocel.
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology