Oct4 Is Required ∼E7.5 for Proliferation in the Primitive Streak

DeVeale, Brian; Brokhman, Irina; Mohseni, Paria; Babak, Tomas; Yoon, Charles; Lin, A. T.; Onishi, Kento; Tomilin, Alexey; Pevny, Larysa; Zandstra, Peter W.; Nagy, András; Kooy, Derek van der

doi:10.1371/journal.pgen.1003957

Cited by 75 publications

(78 citation statements)

References 73 publications

(112 reference statements)

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“…S3, A and B), suggesting that Gata6 might not be the earliest marker of cells on the differentiation path. Nevertheless, our finding is consistent with the importance of Oct4 in cells of the PS region (43,66).…”

Section: Discussionsupporting

confidence: 92%

“…Both Oct4 and Gata6 have been reported to be expressed in the PS region at the gastrulation stage, in addition to their respective distribution in the EPI and VE before gastrulation (31,32,35,43,44). We inferred that Oct4 ϩ Gata6 ϩ cells could be in the PS region of the late-stage E6.5 embryos after gastrulation had begun (embryos VII-X were named E6.5_Late and their EPI was named Late EPI).…”

Section: Gata6mentioning

confidence: 99%

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Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos

Wen

Zeng

Fang

et al. 2017

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 92%

Section: Gata6mentioning

confidence: 99%

Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos

Wen

Zeng

Fang

et al. 2017

Journal of Biological Chemistry

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“…Furthermore, conditional loss-of-function experiments revealed that Oct3/4 is required for normal primitive streak development in gastrulating mouse embryos (DeVeale et al, 2013). In the late phase of reprogramming, which proceeds independently of exogenous reprogramming factor expression, the expression of endogenous OCT3/4 reaches a level similar to that of ESCs and iPSCs.…”

Section: Transient Expression Of Developmental Genes During Reprogrammentioning

confidence: 99%

A developmental framework for induced pluripotency

2015

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During development, cells transition from a pluripotent to a differentiated state, generating all the different types of cells in the body. Development is generally considered an irreversible process, meaning that a differentiated cell is thought to be unable to return to the pluripotent state. However, it is now possible to reprogram mature cells to pluripotency. It is generally thought that reprogramming is accomplished by reversing the natural developmental differentiation process, suggesting that the two mechanisms are closely related. Therefore, a detailed study of cell reprogramming has the potential to shed light on unexplained developmental mechanisms and, conversely, a better understanding of developmental differentiation can help improve cell reprogramming. However, fundamental differences between reprogramming processes and multi-lineage specification during early embryonic development have also been uncovered. In addition, there are multiple routes by which differentiated cells can re-enter the pluripotent state. In this Review, we discuss the connections and disparities between differentiation and reprogramming, and assess the degree to which reprogramming can be considered as a simple reversal of development.

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“…Several studies have shown that Oct4 has explicit lineagespecifying functions (16,(29)(30)(31)(32). Initial reports revealed that ESCs expressing higher Oct4 levels induce differentiation toward the mesoendoderm lineage (33).…”

Section: Pluripotency Factors In Cell Fate Commitmentmentioning

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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Oct4 Is Required ∼E7.5 for Proliferation in the Primitive Streak

Cited by 75 publications

References 73 publications

Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos

Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos

A developmental framework for induced pluripotency

Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation

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