title: Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells.
abstract: The pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians.
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Congras
authors.affiliation: Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31076 Toulouse, France.
authors.forename: Harmonie
authors.initials: H
authors.lastname: Barasc
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Kamila
authors.initials: K
authors.lastname: Canale-Tabet
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Plisson-Petit
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Delcros
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feraud
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.|Service d'hématologie, APHP, GHU Paris Sud, France.
authors.forename: Noufissa
authors.initials: N
authors.lastname: Oudrhiri
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Hadadi
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.|Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Département de biologie et de pathologies médicales, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Griscelli
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.|Service d'hématologie, APHP, GHU Paris Sud, France.|Univ. P. Sud, Univ. Paris Saclay, UFR de Médecine Kremlin Bicêtre, France.
authors.forename: Annelise
authors.initials: A
authors.lastname: Bennaceur-Griscelli
authors.affiliation: Inserm, UMRS935 ESTeam Malignant and Therapeutic Stem Cell Models, F-94800 Villejuif, France.|Univ. P. Sud, Univ. Paris Saclay, UFR de Médecine Kremlin Bicêtre, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Turhan
authors.affiliation: Inserm, U846 Stem Cells and Brain Research Institute, F-69675 Bron, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Afanassieff
authors.affiliation: INRA, UE 1372 GenESI Génétique, Expérimentation et Système Innovants, Surgères, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ferchaud
authors.affiliation: Université de Toulouse INPT ENVT, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31076 Toulouse, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Pinton
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Yerle-Bouissou
authors.affiliation: INRA, UMR 1388 Génétique, Physiologie et Systèmes d'Elevage, F-31326 Castanet-Tolosan, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Acloque
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D043171:Chromosomal Instability; D033481:Chromosomes, Mammalian / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007621:Karyotyping; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc