Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues

Hanna, Jacob; Saha, Krishanu; Jaenisch, Rudolf

doi:10.1016/j.cell.2010.10.008

Cited by 643 publications

(593 citation statements)

References 102 publications

(147 reference statements)

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“…Although the cells we used to carry out this two-phase induction of iPSCs, MEFs, are differentiated cells, they express genes involved in the reprogramming process, such as Klf4 and c-Myc. Previous studies have identified possible intermediate cells derived from other cell types, such as B cells [20,22], although these intermediate cells were not characterized in detail. Thus, this two-phase induction process may be feasible for many other cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, this two-phase induction process may be feasible for many other cell types. Despite significant attention from many researchers, the exact mechanisms by which Yamanaka factors lead to iPSC induction have remained difficult to dissect [20,43,44]. Among the four factors, c-Myc is not necessary for the reprogramming of somatic cells into iPSCs [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…The networks important for ESC pluripotency and self-renewal may not contribute to the iPSC induction, however, as endogenous Nanog is not present at the early phase of reprogramming [17], and the promoters of Oct4 and Sox2 are not available for self-activation, due to DNA methylation [20]. The same genome-wide mapping method has been applied to study the function of Yamanaka factors among ESCs, iPSCs, and what have been termed ''partially reprogrammed cells.''…”

Section: Introductionmentioning

confidence: 99%

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Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

Lin

Perez

Lei³

et al. 2011

Stem Cells

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Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult somatic cells by transduction with Oct4, Sox2, Klf4, and c-Myc, but the molecular cascades initiated by these factors remain poorly understood. Impeding their elucidation is the stochastic nature of the iPS induction process, which results in heterogeneous cell populations. Here we have synchronized the reprogramming process by a two-phase induction: an initial stable intermediate phase following transduction with Oct4, Klf4, and c-Myc, and a final iPS phase following overexpression of Sox2. This approach has enabled us to examine temporal gene expression profiles, permitting the identification of Sox2 downstream genes critical for induction. Furthermore, we have validated the feasibility of our new approach by using it to confirm that downregulation of transforming growth factor b signaling by Sox2 proves essential to the reprogramming process. Thus, we present a novel means for dissecting the details underlying the induction of iPSCs, an approach with significant utility in this arena and the potential for wide-ranging implications in the study of other reprogramming mechanisms. STEM

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

Lin

Perez

Lei³

et al. 2011

Stem Cells

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“…These factors initiate a cascade of events that ultimately lead to reactivation of the endogenous pluripotency genes and the interconnected autoregulatory loop which sustains the pluripotent state (Hanna et al, 2010b). As most master regulators of pluripotency are present in oocytes, preimplantation embryos, ESCs and germ cells, elucidating the mechanism maintaining pluripotency in these systems will help to discover novel inducing factors and improve the efficiency of iPSC generation.…”

Section: Molecular Mechanism Of Reprogramming To Pluripotency the Funmentioning

confidence: 99%

Mechanism and methods to induce pluripotency

Wang

2011

Protein Cell

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Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine.

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“…But there is a general ambiguity associated with the human pluripotent lines isolated so far. Namely, human ESC/iPSC share several important features with mouse stem cells isolated from postimplantation embryo epiblasts, called epiblast embryonic stem cells (EpiESC) [19]. Epiblast stem cells present the next stage in development and therefore have a more limited developmental potential.…”

Section: Introductionmentioning

confidence: 99%