The promise of human induced pluripotent stem cells for research and therapy

Nishikawa, Shin‐Ichi; Goldstein, Robert A.; Nierras, Concepcion R.

doi:10.1038/nrm2466

Cited by 388 publications

(256 citation statements)

References 37 publications

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“…Disease-specific iPSCs may be used to dissect molecular mechanisms of disease progression and develop new pharmaceuticals, whereas patient-specific stem cells may one day provide a resource for autologous cell replacement therapies (Nishikawa et al 2008;Yamanaka 2009). This requires human pluripotent stem cells, however.…”

Section: Human Pluripotent Stem Cellsmentioning

confidence: 99%

Pluripotency in the Embryo and in Culture

Nichols

Smith

2012

Cold Spring Harbor Perspectives in Biology

272

254

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SUMMARYSpecific cells within the early mammalian embryo have the capacity to generate all somatic lineages plus the germline. This property of pluripotency is confined to the epiblast, a transient tissue that persists for only a few days. In vitro, however, pluripotency can be maintained indefinitely through derivation of stem cell lines. Pluripotent stem cells established from the newly formed epiblast are known as embryonic stem cells (ESCs), whereas those generated from later stages are called postimplantation epiblast stem cells (EpiSCs). These different classes of pluripotent stem cell have distinct culture requirements and gene expression programs, likely reflecting the dynamic development of the epiblast in the embryo. In this chapter we review current understanding of how the epiblast forms and relate this to the properties of derivative stem cells. We discuss whether ESCs and EpiSCs are true counterparts of different phases of epiblast development or are culture-generated phenomena. We also consider the proposition that early epiblast cells and ESCs may represent a naïve ground state without any prespecification of lineage choice, whereas later epiblasts and EpiSCs may be primed in favor of particular fates.

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Section: Human Pluripotent Stem Cellsmentioning

confidence: 99%

Pluripotency in the Embryo and in Culture

Nichols

Smith

2012

Cold Spring Harbor Perspectives in Biology

272

254

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“…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]. Among the OSKM factors, Oct4 and Sox2 have been shown to be crucial for cell reprogramming [12,13].…”

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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“…Hacking, 1983) was seen as a field with exceptional therapeutic promise even by those who opposed to it on moral, ethical or religious grounds, the 'discovery' of so-called induced pluripotent stem cells (iPS cells; see Yu et al, 2007;Takahashi, 2007;Cyranoski, 2008;Gottweis and Minger, 2008;Nishikawa et al, 2008;Vrtovec and Scott, 2008) has done away with this consensus. It has opened up the question of whether we need embryonic stem cells at all.…”

Section: Co Mment [Bp4 ]mentioning

confidence: 99%