iPS Cells Can Support Full-Term Development of Tetraploid Blastocyst-Complemented Embryos

Kang, Lan; Wang, Jianle; Zhang, Yu; Kou, Zhaohui; Gao, Shaorong

doi:10.1016/j.stem.2009.07.001

Cited by 432 publications

(310 citation statements)

References 20 publications

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“…Mouse iPS cells have been shown to be successful in homologous recombination [16] and the generation of chimeric [14,17,28] and clonal mice [29,30]. Sheep iPS cells may allow genetic manipulation by homologous recombination, and may be used as the nuclear donor to generate genetically modified sheep through SCNT.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

et al. 2011

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Reprogramming of somatic cells in the enucleated egg made Dolly, the sheep, the first successfully cloned mammal in 1996. However, the mechanism of sheep somatic cell reprogramming has not yet been addressed. Moreover, sheep embryonic stem (ES) cells are still not available, which limits the generation of precise gene-modified sheep. In this study, we report that sheep somatic cells can be directly reprogrammed to induced pluripotent stem (iPS) cells using defined factors (Oct4, Sox2, c-Myc, Klf4, Nanog, Lin28, SV40 large T and hTERT). Our observations indicated that somatic cells from sheep are more difficult to reprogram than somatic cells from other species, in which iPS cells have been reported. We demonstrated that sheep iPS cells express ES cell markers, including alkaline phosphatase, Oct4, Nanog, Sox2, Rex1, stage-specific embryonic antigen-1, TRA-1-60, TRA-1-81 and E-cadherin. Sheep iPS cells exhibited normal karyotypes and were able to differentiate into all three germ layers both in vitro and in teratomas. Our study may help to reveal the mechanism of somatic cell reprogramming in sheep and provide a platform to explore the culture conditions for sheep ES cells. Moreover, sheep iPS cells may be directly used to generate precise gene-modified sheep.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

et al. 2011

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“…Fully reprogrammed induced pluripotent stem cells (iPSCs) are similar to ES cells in terms of their morphology, pluripotency gene expression pattern and ability to form teratomas with all three germ layers. Recently, germline transmission-competent chimeric mice and all-iPSC mice produced via tetraploid complementation have also been reported [3,[7][8][9]. The iPSC technology thus provides a valuable tool for the study of human diseases and holds great potential in cellbased personalized therapy [10,11].…”

Section: Introductionmentioning

confidence: 99%

microRNA-29b is a novel mediator of Sox2 function in the regulation of somatic cell reprogramming

Guo¹,

Liu

Wang

et al. 2012

Cell Res

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Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM), but the mechanisms underlying this reprogramming remain poorly understood. Here, we report that Sox2 directly regulates endogenous microRNA-29b (miR-29b) expression during iPSC generation and that miR-29b expression is required for OSKM-and OSK-mediated reprogramming. Mechanistic studies show that Dnmt3a and Dnmt3b are in vivo targets of miR-29b and that Dnmt3a and Dnmt3b expression is inversely correlated with miR-29b expression during reprogramming. Moreover, the effect of miR-29b on reprogramming can be blocked by Dnmt3a or Dnmt3b overexpression. Further experiments indicate that miR-29b-DNMT signaling is significantly involved in the regulation of DNA methylation-related reprogramming events, such as mesenchymal-to-epithelial transition (MET) and Dlk1-Dio3 region transcription. Thus, our studies not only reveal that miR-29b is a novel mediator of reprogramming factor Sox2 but also provide evidence for a multistep mechanism in which Sox2 drives a miR-29b-DNMT signaling axis that regulates DNA methylation-related events during reprogramming.

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“…Every day in the lab people are worried about getting scooped ». Et voici, en juillet, la publication d'un scoop annoncé, la production de souris entièrement dérivées de cellules iPS, achevant ainsi la démonstration, rigoureuse à souhait maintenant, du caractère pluripotent de ces cellules [7][8][9]. Rien qui ne mérite vraiment publication dans des revues prestigieuses.…”

Section: Ips : Toutes Les Démonstrations Scientifiques Sont-elles Absunclassified

“…C'est ainsi que le caractère pluripotent des cellules ES murines, dérivées de la masse cellulaire interne du blastocyste pré-implantatoire a été démontré, il y a plus de vingt ans [10], ou, plus récemment, celui de cellules ES obtenues après transfert nucléaire. De l'autre, la production de cellules iPS par la technique maintenant classique et « ancienne » de Shinya Yamanaka [11], consistant en l'expression transitoire de quatre facteurs de transcription Oct4/Sox2/Klf4/cMyc à l'aide d'un vecteur viral, les cellules cibles étant, dans les trois articles évoqués ici, des fibroblastes murins embryonnaires [7][8][9]. On sait que ces iPS contribuent à la formation d'animaux chimères viables et fertiles ; restait à démontrer qu'elles avaient strictement les mêmes propriétés que les ES, et donc pouvaient « complémenter » un « embryon tétraploïde ».…”

Section: Ips : Toutes Les Démonstrations Scientifiques Sont-elles Absunclassified

iPS : toutes les démonstrations scientifiques sont-elles absolument nécessaires ?

Chneiweiss

2009

Med Sci (Paris)

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iPS Cells Can Support Full-Term Development of Tetraploid Blastocyst-Complemented Embryos

Cited by 432 publications

References 20 publications

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

microRNA-29b is a novel mediator of Sox2 function in the regulation of somatic cell reprogramming

iPS : toutes les démonstrations scientifiques sont-elles absolument nécessaires ?

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