FGF signalling as a mediator of lineage transitions—Evidence from embryonic stem cell differentiation

Villegas, Santiago Nahuel; Canham, Maurice A.; Brickman, Joshua M.

doi:10.1002/jcb.22536

Cited by 34 publications

(25 citation statements)

References 102 publications

(122 reference statements)

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“…Interestingly, up-regulated genes include a number of transcription factors and proteins such as Id3 that suppress ESC differentiation, and several repressors of FGF/ERK signaling (e.g. Dusp6, Spry4, Spry2, Spred3; Villegas et al, 2010; Ying et al, 2003). …”

Section: Resultsmentioning

confidence: 99%

Pausing of RNA Polymerase II Regulates Mammalian Developmental Potential through Control of Signaling Networks

et al. 2015

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SUMMARY The remarkable capacity for pluripotency and self-renewal in embryonic stem cells (ESCs) requires a finely-tuned transcriptional circuitry wherein the pathways and genes that initiate differentiation are suppressed, but poised to respond rapidly to developmental signals. To elucidate transcriptional control in mouse ESCs in the naïve, ground state, we defined the distribution of engaged RNA polymerase II (Pol II) at high-resolution. We find that promoter-proximal pausing of Pol II is most enriched at genes regulating cell cycle and signal transduction, and not, as expected, at developmental or bivalent genes. Accordingly, ablation of the primary pause-inducing factor NELF does not increase expression of lineage markers, but instead causes proliferation defects, embryonic lethality and dysregulation of ESC signaling pathways. Indeed, ESCs lacking NELF have dramatically attenuated FGF/ERK activity, rendering them resistant to differentiation. This work thus uncovers a key role for NELF-mediated pausing in establishing the responsiveness of stem cells to developmental cues.

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Section: Resultsmentioning

confidence: 99%

Pausing of RNA Polymerase II Regulates Mammalian Developmental Potential through Control of Signaling Networks

et al. 2015

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“…3A), suggesting their role in early embryogenesis and development (42)(43)(44)(45). Earlier, we showed that increased expression of uPAR with IR treatment induces the angiogenic ability of medulloblastoma cells (7,44).…”

Section: Mol Cancer Ther; 13(5) May 2014mentioning

confidence: 88%

Nuclear Translocation of Hand-1 Acts as a Molecular Switch to Regulate Vascular Radiosensitivity in Medulloblastoma Tumors: The Protein uPAR Is a Cytoplasmic Sequestration Factor for Hand-1

Asuthkar

Gogineni

Rao

et al. 2014

Molecular Cancer Therapeutics

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Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in the tumor-stromal invasive microenvironment in many human cancers, including medulloblastoma. The role of uPAR in tumor progression and angiogenesis has been well characterized. Previously, in medulloblastoma cells, we showed that ionizing radiation (IR)-induced uPAR is a potent activator of cancer stem cell (CSC)-like properties and is associated with various transcription factors that are involved during embryonic development and cancer. In the present study, we show that uPAR protein acts as a cytoplasmic sequestration factor for a novel basic helixloop-helix transcription factor, Hand-1. The Hand-1 protein plays an essential role in the differentiation of trophoblast giant cells and cardiac morphogenesis, and yet its precise cellular function and its contribution to cancer remain mostly unknown. We also observed that the Hand-1 protein is upregulated in uPAR short hairpin RNA-treated medulloblastoma cells and accompanies sustained cell growth and angiogenesis. Furthermore, IR-induced uPAR overexpression negatively regulates Hand-1 activity and results in the stabilization of angiogenesis-promoting molecules, including hypoxia-inducible factor-1a. Finally, uPAR overexpression and its association with Hand-1 after IR treatment indicate that uPAR is capable of regulating Hand-1 and that uPAR has a role in the process of IR-induced tumor angiogenesis.

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“…stimulation of transcription of the pluripotency genes) as well as in indirect manner (e.g. stimulating the feeder layer cells) [76,77].…”

Section: Signalling Mediated By Erk1/2mentioning

confidence: 99%

Of mice and men – differential mechanisms of maintaining the undifferentiated state in mESC and hESC

Arabadjiev¹,

Petkova²,

Momchilova³

et al. 2012

Biodiscovery

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FGF signalling as a mediator of lineage transitions—Evidence from embryonic stem cell differentiation

Cited by 34 publications

References 102 publications

Pausing of RNA Polymerase II Regulates Mammalian Developmental Potential through Control of Signaling Networks

Pausing of RNA Polymerase II Regulates Mammalian Developmental Potential through Control of Signaling Networks

Nuclear Translocation of Hand-1 Acts as a Molecular Switch to Regulate Vascular Radiosensitivity in Medulloblastoma Tumors: The Protein uPAR Is a Cytoplasmic Sequestration Factor for Hand-1

Of mice and men – differential mechanisms of maintaining the undifferentiated state in mESC and hESC

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