Cell signaling and transcription factors regulating cell fate during formation of the mouse blastocyst

Frum, Tristan; Ralston, Amy

doi:10.1016/j.tig.2015.04.002

Cited by 100 publications

(88 citation statements)

References 85 publications

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“…Initially, the ICM contains a mixture of cells that express high or low Nanog, but this tissue subsequently sorts into the Nanog-positive, pluripotent epiblast and Nanog-negative primitive endoderm by the late blastocyst stage (Morgani and Brickman, 2014). Soon afterward, blastocysts hatch and implant into the uterine wall, completing pre-implantation development (Frum and Ralston, 2015). …”

Section: Introduction To Mammalian Pre-implantation Developmentmentioning

confidence: 99%

Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

Davis

Rebay

2017

Developmental Biology

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Among the mechanisms that steer cells to their correct fate during normal development, master regulatory networks are unique in their sufficiency to trigger a developmental program outside of its normal context. In this review we discuss the key features that underlie master regulatory potency during normal and ectopic development, focusing on two examples, the retinal determination gene network (RDGN) that directs eye development in the fruit fly and the pluripotency gene network (PGN) that maintains cell fate competency in the early mammalian embryo. In addition to the hierarchical transcriptional activation, extensive positive transcriptional feedback, and cooperative protein-protein interactions that enable master regulators to override competing cellular programs, recent evidence suggests that network topology must also be dynamic, with extensive rewiring of the interactions and feedback loops required to navigate the correct sequence of developmental transitions to reach a final fate. By synthesizing the in vivo evidence provided by the RDGN with the extensive mechanistic insight gleaned from the PGN, we highlight the unique regulatory capabilities that continual reorganization into new hierarchies confers on master control networks. We suggest that deeper understanding of such dynamics should be a priority, as accurate spatiotemporal remodeling of network topology will undoubtedly be essential for successful stem cell based therapeutic efforts.

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Section: Introduction To Mammalian Pre-implantation Developmentmentioning

confidence: 99%

Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

Davis

Rebay

2017

Developmental Biology

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“…Gene regulatory networks driven by master transcription factors (TFs) play pivotal roles over a large spectrum of biological processes, from adaptive cell responses (Shinozaki et al, 2003) to cell fate specification during development (Davidson et al, 2002). The key properties of TF networks, shared among cell types, developmental contexts and organisms (Huang et al, 2005), are exemplified by the pluripotency network, which plays a dominant role during early mammalian embryogenesis (Frum and Ralston, 2015). The robustness of this network allows the capture ex vivo of the transient biological identity of the pluripotent epiblast through the derivation of self-renewing Embryonic Stem (ES) cells (Parfitt and Shen, 2014), which have enabled identification of key TFs (e.g.…”

Section: Introductionmentioning

confidence: 99%

The molecular logic of Nanog-induced self-renewal

Heurtier

Owens

González

et al. 2018

Preprint

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rue du docteur Roux, Paris 75015. a Equal contributionTranscription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only very partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.

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“…In the mouse, over the first ∼2.5 days of development (∼E2.5), cleavage of the zygote results in the formation of the 8–16 cell morula. The cells located on the surface of the morula acquire TE identity, whereas cells located on the inside of the morula comprise the inner cell mass (ICM), which gives rise to the PrE and EPI (reviewed in refs 13, 14). …”

mentioning

confidence: 99%

Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst

et al. 2016

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Intercellular communication is essential to coordinate the behaviour of individual cells during organismal development. The preimplantation mammalian embryo is a paradigm of tissue self-organization and regulative development; however, the cellular basis of these regulative abilities has not been established. Here we use a quantitative image analysis pipeline to undertake a high-resolution, single-cell level analysis of lineage specification in the inner cell mass (ICM) of the mouse blastocyst. We show that a consistent ratio of epiblast and primitive endoderm lineages is achieved through incremental allocation of cells from a common progenitor pool, and that the lineage composition of the ICM is conserved regardless of its size. Furthermore, timed modulation of the FGF-MAPK pathway shows that individual progenitors commit to either fate asynchronously during blastocyst development. These data indicate that such incremental lineage allocation provides the basis for a tissue size control mechanism that ensures the generation of lineages of appropriate size.

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Cell signaling and transcription factors regulating cell fate during formation of the mouse blastocyst

Cited by 100 publications

References 85 publications

Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks

The molecular logic of Nanog-induced self-renewal

Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst

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