Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells

Jan Ole Bertelsen Secher; Ahmet  Ceylan; Gianluca Mazzoni; Kaveh Mashayekhi-Nezamabadi; Tong Li; Suchitra Muenthaisong; Troels Nielsen; Dong Li; Shengting Li; Stoyan Gueorguiev Petkov; Susanna Cirera Salicio; Yonglun Luo; Lori Thombs; Haja Kadarmideen; András Dinnyés; Lars Bolund; Bernard Aj Roelen; Mette Schmidt; Henrik Callesen; Poul Hyttel; Kristine Freude

doi:10.1002/mrd.22771

Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells

Jan Ole Bertelsen Secher, Ahmet Ceylan, Gianluca Mazzoni, Kaveh Mashayekhi-Nezamabadi, Tong Li, Suchitra Muenthaisong, Troels Nielsen, Dong Li, Shengting Li, Stoyan Gueorguiev Petkov, Susanna Cirera Salicio, Yonglun Luo, Lori Thombs, Haja Kadarmideen, András Dinnyés, Lars Bolund, Bernard Aj Roelen, Mette Schmidt, Henrik Callesen, Poul HyttelKristine Freude

10 Citations (Scopus)

Abstract

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 extent, 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. 84: 229–245, 2017.

Original language	English
Journal	Molecular Reproduction and Development
Volume	84
Issue number	3
Pages (from-to)	229-245
ISSN	1040-452X
DOIs	https://doi.org/10.1002/mrd.22771
Publication status	Published - 1 Mar 2017

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Secher, J. O. B., Ceylan, A., Mazzoni, G., Mashayekhi-Nezamabadi, K., Li, T., Muenthaisong, S., Nielsen, T., Li, D., Li, S., Petkov, S. G., Cirera Salicio, S., Luo, Y., Thombs, L., Kadarmideen, H., Dinnyés, A., Bolund, L., Roelen, B. A., Schmidt, M., Callesen, H., ... Freude, K. (2017). Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells. Molecular Reproduction and Development, 84(3), 229-245. https://doi.org/10.1002/mrd.22771

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 et al.
In: Molecular Reproduction and Development, Vol. 84, No. 3, 01.03.2017, p. 229-245.

Research output: Contribution to journal › Journal article › Research › peer-review

Secher, JOB, Ceylan, A, Mazzoni, G , Mashayekhi-Nezamabadi, K , Li, T, Muenthaisong, S, Nielsen, T, Li, D, Li, S, Petkov, SG, Cirera Salicio, S, Luo, Y, Thombs, L, Kadarmideen, H, Dinnyés, A, Bolund, L, Roelen, BA, Schmidt, M, Callesen, H, Hyttel, P & Freude, K 2017, 'Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells', Molecular Reproduction and Development, vol. 84, no. 3, pp. 229-245. https://doi.org/10.1002/mrd.22771

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title = "Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells",

abstract = "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 extent, 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. 84: 229–245, 2017.",

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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 - 2017/3/1

Y1 - 2017/3/1

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 extent, 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. 84: 229–245, 2017.

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 extent, 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. 84: 229–245, 2017.

U2 - 10.1002/mrd.22771

DO - 10.1002/mrd.22771

M3 - Journal article

C2 - 28044390

SN - 1040-452X

VL - 84

SP - 229

EP - 245

JO - Molecular Reproduction and Development

JF - Molecular Reproduction and Development

IS - 3

ER -

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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