Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System

Wu, Zhao; Chen, Ji‐Jun; Ren, Jiangtao; Bao, Lei; Liao, Jing; Cui, Chun; Rao, Linjun; Li, Hui; Gu, Yijun; Dai, Huiming; Zhu, Hui; Teng, Xiaokun; Cheng, Lü; Xiao, Lei

doi:10.1093/jmcb/mjp003

Cited by 338 publications

(164 citation statements)

References 41 publications

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“…Since the first discovery that four transcriptional factors could reprogram somatic cells into iPS cells in mice, essentially similar strategies have been applied successfully to human, rat, primate, and porcine cells (3,4,(12)(13)(14)(15)38). The present study for the first time has demonstrated generation of iPS cells in the rabbit, with a long history as a non-rodent laboratory animal species.…”

Section: Discussionmentioning

confidence: 82%

“…However, any direct extrapolation of such results to humans is problematic because mice differ considerably from humans in their physiology and life span, and the pluripotency regulatory systems also differ between mouse and human iPS cells (10). In addition to mouse iPS cells, monkey and pig iPS cells were established successfully in several laboratories (11)(12)(13)(14)(15). As expected, the iPS cells from these two species resemble human iPS cells more than do the mouse cells and thus should provide superior experimental models to assess therapeutic applications of iPS cells.…”

mentioning

confidence: 99%

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Generation of Induced Pluripotent Stem Cells in Rabbits

Honda

Hirose

Hatori

et al. 2010

Journal of Biological Chemistry

153

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Human induced pluripotent stem (iPS) cells have the potential to establish a new field of promising regenerative medicine. Therefore, the safety and the efficiency of iPS-derived cells must be tested rigorously using appropriate animal models before human trials can commence. Here, we report the establishment of rabbit iPS cells as the first human-type iPS cells generated from a small laboratory animal species. Using lentiviral vectors, four human reprogramming genes (c-MYC, KLF4, SOX2, and OCT3/4) were introduced successfully into adult rabbit liver and stomach cells. The resulting rabbit iPS cells closely resembled human iPS cells; they formed flattened colonies with sharp edges and proliferated indefinitely in the presence of basic FGF. They expressed the endogenous pluripotency markers c-MYC, KLF4, SOX2, OCT3/4, and NANOG, whereas the introduced human genes were completely silenced. Using in vitro differentiating conditions, rabbit iPS cells readily differentiated into ectoderm, mesoderm, and endoderm. They also formed teratomas containing a variety of tissues of all three germ layers in immunodeficient mice. Thus, the rabbit iPS cells fulfilled all of the requirements for the acquisition of the fully reprogrammed state, showing high similarity to their embryonic stem cell counterparts we generated recently. However, their global gene expression analysis revealed a slight but rigid difference between these two types of rabbit pluripotent stem cells. The rabbit model should enable us to compare iPS cells and embryonic stem cells under the same standardized conditions in evaluating their ultimate feasibility for pluripotent cell-based regenerative medicine in humans.

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Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

Generation of Induced Pluripotent Stem Cells in Rabbits

Honda

Hirose

Hatori

et al. 2010

Journal of Biological Chemistry

153

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“…However, naïve pig pluripotent cells had proven to be particularly difficult to establish from the pig blastocyst (Telugu et al 2010). Recent studies reported that a widened range of differentiated cells could be converted to iPS cells by introduction of reprogramming factors, which provided a new method to establish pig pluripotential cells (Takahashi & Yamanaka 2006, Takahashi et al 2007, Ezashi et al 2009, Wu et al 2009. Therefore, in our study, reprogramming procedures developed for human iPS cells establishment had also been adapted to iPPCs.…”

Section: Discussionmentioning

confidence: 99%

“…The generation of pig pluripotent cells would provide a new and effective cell source for inducing the NSCs. In vitro studies had demonstrated that the pig pluripotent cells were able to be differentiated into three germ layers after suspension culture (Wu et al 2009), suggesting a potential for multiple lineage differentiation. However, the neural lineage-specific differentiation of pig pluripotent cells had not been reported.…”

Section: Introductionmentioning

confidence: 99%

Generation of neural progenitors from induced Bama miniature pig pluripotent cells

Shan²,

Wu³

et al. 2014

Reproduction

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Pig pluripotent cells may represent an advantageous experimental tool for developing therapeutic application in the human biomedical field. However, it has previously been proven to be difficult to establish from the early embryo and its pluripotency has not been distinctly documented. In recent years, induced pluripotent stem (iPS) cell technology provides a new method of reprogramming somatic cells to pluripotent state. The generation of iPS cells together with or without certain small molecules has become a routine technique. However, the generation of iPS cells from pig embryonic tissues using viral infections together with small molecules has not been reported. Here, we reported the generation of induced pig pluripotent cells (iPPCs) using the iPS technology in combination with valproic acid (VPA). VPA treatment significantly increased the expression of pluripotent genes and played an important role in early reprogramming. We showed that iPPCs resembled pig epiblast cells in their morphology and pluripotent markers, such as OCT4, NANOG, and SSEA1. It had a normal karyotype and could form embryoid bodies, which express three germ layer markers in vitro. In addition, the iPPCs might directly differentiate into neural progenitors after being induced with the retinoic acid and extracellular matrix. Our study established a reasonable method to generate pig pluripotent cells, which might be a new donor cell source for human neural disease therapy.

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“…However, transgenic technologies are not as widely available in these species as in mice where the techniques for gene targeting and pronuclear injection are well developed and widely available. Indeed, many of the methods for genetic manipulation used in the mouse are not routine or even presently possible in other mammalian species, although the recent development of rat and pig ES cells creates the potential that gene targeting may be extended to these species (Buehr et al 2008;Wu et al 2009). The generation of knockout, knockin and humanized rats is also being pursued using nuclear transplantation of genetically modified somatic cells (Zhou et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Animal transgenesis: an overview

2009

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Transgenic animals are extensively used to study in vivo gene function as well as to model human diseases. The technology for producing transgenic animals exists for a variety of vertebrate and invertebrate species. The mouse is the most utilized organism for research in neurodegenerative diseases. The most commonly used techniques for producing transgenic mice involves either the pronuclear injection of transgenes into fertilized oocytes or embryonic stem cell-mediated gene targeting. Embryonic stem cell technology has been most often used to produce null mutants (gene knockouts) but may also be used to introduce subtle genetic modifications down to the level of making single nucleotide changes in endogenous mouse genes. Methods are also available for inducing conditional gene knockouts as well as inducible control of transgene expression. Here, we review the main strategies for introducing genetic modifications into the mouse, as well as in other vertebrate and invertebrate species. We also review a number of recent methodologies for the production of transgenic animals including retrovirus-mediated gene transfer, RNAi-mediated gene knockdown and somatic cell mutagenesis combined with nuclear transfer, methods that may be more broadly applicable to species where both pronuclear injection and ES cell technology have proven less practical.

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Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System

Cited by 338 publications

References 41 publications

Generation of Induced Pluripotent Stem Cells in Rabbits

Generation of Induced Pluripotent Stem Cells in Rabbits

Generation of neural progenitors from induced Bama miniature pig pluripotent cells

Animal transgenesis: an overview

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