title: Generation of feeder-free pig induced pluripotent stem cells without Pou5f1.
abstract: The pig represents an ideal large-animal model, intermediate between rodents and humans, for the preclinical assessment of emerging cell therapies. As no validated pig embryonic stem (pES) cell lines have been derived so far, pig induced pluripotent stem cells (piPSCs) should offer  an alternative source of undifferentiated cells to advance regenerative medicine research from bench to clinical trial. We report here for the first time the derivation of piPSCs from adult fibroblast with only three transcription factors: Sox2 (sex determining region Y-box 2), Klf4 (Krüppel-like  factor 4), and c-Myc (avian myelocytomatosis viral oncogene homolog). We have been able to demonstrate that exogenous Pou5f1 (POU domain class 5 transcription factor 1; abbreviated as Octamer-4: Oct4) is dispensable to achieve and maintain pluripotency in the generation of piPSCs. To the best  of our knowledge, this is also the first report of somatic reprogramming in any species without the overexpression, either directly or indirectly, of Oct4. Moreover, we were able to generate piPSCs without the use of feeder cells, approaching thus xeno-free conditions. Our work paves the way  for the derivation of clinical grade piPSCs for regenerative medicine.
authors.affiliation: Center for Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Montserrat
authors.forename: Lorena
authors.initials: L
authors.lastname: de Oñate
authors.forename: Elena
authors.initials: E
authors.lastname: Garreta
authors.forename: Federico
authors.initials: F
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Adamo
authors.forename: Cristina
authors.initials: C
authors.lastname: Eguizábal
authors.forename: Sophia
authors.initials: S
authors.lastname: Häfner
authors.forename: Rita
authors.initials: R
authors.lastname: Vassena
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D061252:Feeder Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D044968:Regenerative Medicine; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors