TY - JOUR
T1 - Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells
AU - Congras, Annabelle
AU - Barasc, Harmonie
AU - Canale-Tabet, Kamila
AU - Plisson-Petit, Florence
AU - Delcros, Chantal
AU - Feraud, Olivier
AU - Oudrhiri, Noufissa
AU - Hadadi, Eva
AU - Griscelli, Franck
AU - Bennaceur-Griscelli, Annelise
AU - Turhan, Ali
AU - Afanassieff, Marielle
AU - Ferchaud, Stéphane
AU - Pinton, Alain
AU - Yerle-Bouissou, Martine
AU - Acloque, Hervé
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84973333429&partnerID=8YFLogxK
U2 - 10.1038/srep27059
DO - 10.1038/srep27059
M3 - Article
C2 - 27245508
AN - SCOPUS:84973333429
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 27059
ER -