An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells

Kim, Jonghwan; Jh, Chu; Shen, Xiaohua; Wang, Jianlong; Orkin, Stuart H.

doi:10.1016/j.cell.2008.02.039

Cited by 1,238 publications

(1,203 citation statements)

References 66 publications

(126 reference statements)

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“…Multiple Klfs are implicated in several processes, such as adipogenesis (13-15, 43, 52, 53) and stem cell maintenance (16,17). Our results, together with recent results in stem cells and fibroblasts, suggest that feedback regulation and redundancy may occur within the Klf family, such that Klfs, 1, 2, 4, and 5, may (depending on which is present in which tissue) activate Klfs 3 and 8, and Klfs 3 and 8 may then feedback to temper the activation.…”

Section: Discussionmentioning

confidence: 99%

A Network of Krüppel-like Factors (Klfs)

Eaton¹,

Funnell²,

Sue³

et al. 2008

Journal of Biological Chemistry

100

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Section: Discussionmentioning

confidence: 99%

A Network of Krüppel-like Factors (Klfs)

Eaton¹,

Funnell²,

Sue³

et al. 2008

Journal of Biological Chemistry

100

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“…Transcription of genes encoding epigenetic factors such as Polycomb proteins (i.e., Eed, Jarid2, and Cbx7), Polycomb-associated proteins (Max), and members of the MLL complexes (Wdr5 and Ash2l) appears to be under the control of the pluripotency network (22, 25,65), and their expression is positively regulated by the OSN proteins.…”

Section: Cross Talk Between Pluripotency and Epigenetic Factorsmentioning

confidence: 99%

Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation

Morey

Santanach

Croce

2015

Molecular and Cellular Biology

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c Embryonic stem cells (ESCs) are characterized by their ability to self-renew and to differentiate into all cell types of a given organism. Understanding the molecular mechanisms that govern the ESC state is of great interest not only for basic research-for instance, ESCs represent a perfect system to study cellular differentiation in vitro-but also for their potential implications in human health, as these mechanisms are likewise involved in cancer progression and could be exploited in regenerative medicine. In this minireview, we focus on the latest insights into the molecular mechanisms mediated by the pluripotency factors as well as their roles during differentiation. We also discuss recent advances in understanding the function of the epigenetic regulators, Polycomb and MLL complexes, in ESC biology. Within 2 days after fertilization, a mouse oocyte has undergone a series of cellular divisions and has developed into the morula embryo. The totipotent cells within the morula then divide and further specialize to form the hollow blastocyst sphere. The outer layer of the blastocyst contains the trophectoderm cells, while the inner cell mass (ICM) contains the pluripotent embryonic stem cells (ESCs) that will give rise in the developing embryo to all cell types of the three germ layers-ectoderm, mesoderm, and endoderm. Mouse ESCs were first isolated by Evans and Kaufman in 1981 (1) and have since been extensively studied. Under proper cell culture conditions, ESCs can divide and self-renew indefinitely, yet under differentiation stimuli, ESCs can also differentiate into virtually all cell types of the organism.Which molecular mechanisms control the decision of ESCs to self-renew or to differentiate? During the last decades, several transcription factors have been identified to be essential for ESC pluripotency. These transcription factors regulate pluripotency by a so-called "pluripotency network" that regulates their own expression and coregulates the expression of other key transcription factors through multiple mechanisms. Interestingly, pluripotency is controlled at the transcriptional levels of genes through specific signaling pathways and epigenetic factors.Epigenetics is the study of heritable changes in gene expression that are not caused by changes at the DNA sequence level. The Polycomb and MLL (myeloid-lineage leukemia) complexes are two of the best-characterized epigenetic machineries implicated in ESC pluripotency and differentiation. Although pluripotency factors do not physically interact with Polycomb and MLL complexes, they coregulate lineage-specific genes important for ESC differentiation.In this review, we discuss the most recent advances in understanding mouse ESC pluripotency and differentiation, paying particular attention to Oct4, Nanog, and Sox2, as well as to factors involved in the exit from pluripotency. Finally, we discuss the function and the molecular mechanisms of the Polycomb and MLL complexes in mouse ESC pluripotency. MASTER REGULATORS OF ESC IDENTITY: THE Oct4, Sox2, AND Nano...

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“…Nr0b1/Dax1 is an orphan nuclear hormone receptor that co-occupies many gene promoters together with other pluripotency factors, such as Nanog, Sox2 and Klf4 [52]. Nr0b1/ Dax1 overexpression blocks differentiation, but does neither affect expression of other pluripotency factors such as Nanog and Esrrb, nor phosphorylation levels of Erk [48,49].…”

Section: (D) Tfe3mentioning

confidence: 99%

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Schulz

2017

Phil. Trans. R. Soc. B

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Already during early embryogenesis, before sex-specific hormone production is initiated, sex differences in embryonic development have been observed in several mammalian species. Typically, female embryos develop more slowly than their male siblings. A similar phenotype has recently been described in differentiating murine embryonic stem cells, where a double dose of the X-chromosome halts differentiation until dosage-compensation has been achieved through X-chromosome inactivation. On the molecular level, several processes associated with early differentiation of embryonic stem cells have been found to be affected by X-chromosome dosage, such as the transcriptional state of the pluripotency network, the activity pattern of several signal transduction pathways and global levels of DNA-methylation. This review provides an overview of the sex differences described in embryonic stem cells from mice and discusses a series of X-linked genes that are associated with pluripotency, signalling and differentiation and their potential involvement in mediating the observed X-dosage–dependent effects. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

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An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells

Cited by 1,238 publications

References 66 publications

A Network of Krüppel-like Factors (Klfs)

A Network of Krüppel-like Factors (Klfs)

Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

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