Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells
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Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells. / Secher, Jan Ole Bertelsen; Ceylan, Ahmet ; Mazzoni, Gianluca; Mashayekhi-Nezamabadi, Kaveh; Li, Tong; Muenthaisong, Suchitra; Nielsen, Troels; Li, Dong; Li, Shengting; Petkov, Stoyan Gueorguiev; Cirera Salicio, Susanna; Luo, Yonglun; Thombs, Lori; Kadarmideen, Haja; Dinnyés, András; Bolund, Lars; Roelen, Bernard Aj; Schmidt, Mette; Callesen, Henrik; Hyttel, Poul; Freude, Kristine.
In: Molecular Reproduction and Development, Vol. 84, No. 3, 2017, p. 229-245.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells
AU - Secher, Jan Ole Bertelsen
AU - Ceylan, Ahmet
AU - Mazzoni, Gianluca
AU - Mashayekhi-Nezamabadi, Kaveh
AU - Li, Tong
AU - Muenthaisong, Suchitra
AU - Nielsen, Troels
AU - Li, Dong
AU - Li, Shengting
AU - Petkov, Stoyan Gueorguiev
AU - Cirera Salicio, Susanna
AU - Luo, Yonglun
AU - Thombs, Lori
AU - Kadarmideen, Haja
AU - Dinnyés, András
AU - Bolund, Lars
AU - Roelen, Bernard Aj
AU - Schmidt, Mette
AU - Callesen, Henrik
AU - Hyttel, Poul
AU - Freude, Kristine
PY - 2017
Y1 - 2017
N2 - Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF-derived piPSCs were more successful than their FGF-derived counterparts in the generation of in vitro chimeras and in teratoma formation. When LIF piPSCs chimeras were transferred into surrogate sows and allowed to develop, only their prescence within the embryonic membranes could be detected. Whole transcriptome analysis of the piPSCs and porcine neonatal fibroblasts showed that they clustered together, but apart from the two pluripotent cell populations of early porcine embryos, indicating incomplete reprogramming. Indeed, bioinformatic analysis of the pluripotency-related gene network of the LIF- versus FGF-derived piPSCs revealed that ZFP42 (REX1) expression was absent in both piPSC-like cells, whereas it was expressed in the porcine inner cell mass at Day 7/8. A second striking difference was the expression of ATOH1 in piPSC-like cells, which was absent in the inner cell mass. Moreover, our gene expression analyses plus correlation analyses of known pluripotency genes identified unique relationships between pluripotency genes in the inner cell mass, which are to some extend, in the piPSC-like cells. This deficiency in downstream gene activation and divergent gene expression may be underlie the inability to derive germ line-transmitting piPSCs, and provides unique insight into which genes are necessary to achieve fully reprogrammed piPSCs.
AB - Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF-derived piPSCs were more successful than their FGF-derived counterparts in the generation of in vitro chimeras and in teratoma formation. When LIF piPSCs chimeras were transferred into surrogate sows and allowed to develop, only their prescence within the embryonic membranes could be detected. Whole transcriptome analysis of the piPSCs and porcine neonatal fibroblasts showed that they clustered together, but apart from the two pluripotent cell populations of early porcine embryos, indicating incomplete reprogramming. Indeed, bioinformatic analysis of the pluripotency-related gene network of the LIF- versus FGF-derived piPSCs revealed that ZFP42 (REX1) expression was absent in both piPSC-like cells, whereas it was expressed in the porcine inner cell mass at Day 7/8. A second striking difference was the expression of ATOH1 in piPSC-like cells, which was absent in the inner cell mass. Moreover, our gene expression analyses plus correlation analyses of known pluripotency genes identified unique relationships between pluripotency genes in the inner cell mass, which are to some extend, in the piPSC-like cells. This deficiency in downstream gene activation and divergent gene expression may be underlie the inability to derive germ line-transmitting piPSCs, and provides unique insight into which genes are necessary to achieve fully reprogrammed piPSCs.
U2 - 10.1002/mrd.22771
DO - 10.1002/mrd.22771
M3 - Journal article
C2 - 28044390
VL - 84
SP - 229
EP - 245
JO - Molecular Reproduction and Development
JF - Molecular Reproduction and Development
SN - 1040-452X
IS - 3
ER -
ID: 173281590