Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells

Annabelle Congras, Harmonie Barasc, Kamila Canale-Tabet, Florence Plisson-Petit, Chantal Delcros, Olivier Feraud, Noufissa Oudrhiri, Eva Hadadi, Franck Griscelli, Annelise Bennaceur-Griscelli, Ali Turhan, Marielle Afanassieff, Stéphane Ferchaud, Alain Pinton, Martine Yerle-Bouissou, Hervé Acloque

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Article number27059
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 1 Jun 2016
Externally publishedYes

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