Network Features and Dynamical Landscape of Naive and Primed Pluripotency

Pfeuty, Benjamin; Kress, Clémence; Pain, Bertrand

doi:10.1016/j.bpj.2017.10.033

Cited by 13 publications

(11 citation statements)

References 97 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This GRN regulates pluripotency by repressing genes involved in differentiation and activating other genes important for pluripotency (Navarro et al, 2012; Thomson et al, 2011). The same GRN also initiates the process of exiting pluripotency by responding to extrinsic and intrinsic signals and changing the regulatory regions and partners these factors bind to (Hoffman et al, 2013; Kalkan and Smith, 2014; Mohammed et al, 2017; Pfeuty et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

et al. 2019

View full text Add to dashboard Cite

Pluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development is its expression restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation..

show abstract

Section: Introductionmentioning

confidence: 99%

Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The main characteristics of pluripotent stem cells in both states, such as the expression of core transcription factors Oct4, Nanog, and Sox2, cell cycle structures and multilineage differentiation potential, are significantly similar, whereas other characteristics, such as germ line transmission in chimeric embryos, X-chromosome inactivation and single-cell viability/clonogenicity substantially differ [139,140]. For the maintenance of pluripotent states and self-renewal, intrinsic core transcription factors Nanog, Oct4, Sox2, Esrrb, and Klf4 form an autoregulatory circuit, which is supported by extrinsic signaling factors [141][142][143]. However, naїve and primed pluripotent stem cells are maintained in different in vitro systems supporting adequate configurations of their gene regulatory network that simultaneously ensure their identity, stimulate self-renewal and inhibit differentiation.…”

Section: Tgfβ Family In Signaling Network Of Naїve and Primed Pluripotent Stem Cellsmentioning

confidence: 99%

TGFβ Family Signaling Pathways in Pluripotent and Teratocarcinoma Stem Cells’ Fate Decisions: Balancing Between Self-Renewal, Differentiation, and Cancer

Gordeeva

2019

Cells

View full text Add to dashboard Cite

The transforming growth factor-β (TGFβ) family factors induce pleiotropic effects and are involved in the regulation of most normal and pathological cellular processes. The activity of different branches of the TGFβ family signaling pathways and their interplay with other signaling pathways govern the fine regulation of the self-renewal, differentiation onset and specialization of pluripotent stem cells in various cell derivatives. TGFβ family signaling pathways play a pivotal role in balancing basic cellular processes in pluripotent stem cells and their derivatives, although disturbances in their genome integrity induce the rearrangements of signaling pathways and lead to functional impairments and malignant transformation into cancer stem cells. Therefore, the identification of critical nodes and targets in the regulatory cascades of TGFβ family factors and other signaling pathways, and analysis of the rearrangements of the signal regulatory network during stem cell state transitions and interconversions, are key issues for understanding the fundamental mechanisms of both stem cell biology and cancer initiation and progression, as well as for clinical applications. This review summarizes recent advances in our understanding of TGFβ family functions in naїve and primed pluripotent stem cells and discusses how these pathways are involved in perturbations in the signaling network of malignant teratocarcinoma stem cells with impaired differentiation potential.

show abstract

“…Esrrb is an orphan nuclear receptor that is required for self-renewal and pluripotency of ESCs 33 . In ESCs, Esrrb function is controlled by extrinsic cues mediated by kinases such as GSK3i 34 and intrinsic regulators such as Nanog 35 .…”

Section: Introductionmentioning

confidence: 99%

Esrrbis a cell cycle dependent XEN priming factor balancing between pluripotency and differentiation

Levi

Arnon

Feldman

et al. 2020

Preprint

View full text Add to dashboard Cite

Cell cycle and differentiation decisions are tightly linked; however, the underlying principles that drive these decisions are not fully understood. Here, we combined cell-cycle reporter system and single-cell RNA-seq profiling to study the transcriptomes of mouse embryonic stem cells (ESCs) in the context of cell cycle states and differentiation. By applying a retinoic acid-based protocol as a differentiation assay representing exit from pluripotency, we show that Esrrb, a key pluripotent factor is upregulated during G2/M phase and promptly downregulated during exit from pluripotency. Enhancer chromatin states and Esrrb ChIP-seq map expose Esrrb's association with differentiation genes, were in the context of retinoic acid, enhancers associated with differentiation program driving extraembryonic endoderm cells (XENs). We show that only G2/M ESCs were capable of differentiating into XENs, whereas cells in the G1 phase predominantly produce epiblast stem cells (EpiSCs). Furthermore, Cells engineered to overexpress Esrrb allowed G1 ESCs to produce XENs, while Esrrb knockout ESCs completely lost their potential to differentiate into XEN. Interestingly, this phenomenon is unique to the pluripotency state as sorting cells after initiation of differentiation resulted in a cell cycle-independent differentiation decisions. Cells in both G1 and G2/M phases contributed equally to EpiSC and XEN cellular lineages. Taken together, this study reveals an important functional link between Esrrb and cell-cycle states during exit from pluripotency. Our novel approach of applying single cell RNAseq in a cell cycle dependent manner can be further expand into other differentiation assays and expand our understanding of early differentiation events.

show abstract

Network Features and Dynamical Landscape of Naive and Primed Pluripotency

Cited by 13 publications

References 97 publications

Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

TGFβ Family Signaling Pathways in Pluripotent and Teratocarcinoma Stem Cells’ Fate Decisions: Balancing Between Self-Renewal, Differentiation, and Cancer

Esrrbis a cell cycle dependent XEN priming factor balancing between pluripotency and differentiation

Contact Info

Product

Resources

About