title: Reprogramming of human fibroblasts to pluripotency with lineage specifiers.
abstract: 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.
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Montserrat
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nivet
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sancho-Martinez
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hishida
authors.forename: Sachin
authors.initials: S
authors.lastname: Kumar
authors.forename: Laia
authors.initials: L
authors.lastname: Miquel
authors.forename: Carme
authors.initials: C
authors.lastname: Cortina
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Hishida
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Concepcion Rodriguez
authors.initials: CR
authors.lastname: Esteban
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D054337:Cell Dedifferentiation / Q000235:genetics; D019070:Cell Lineage; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D005347:Fibroblasts / Q000502:physiology*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D048091:Guided Tissue Regeneration; D006801:Humans; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse