Activation of the canonical Wnt signaling pathway synergizes with leukemia inhibitory factor (LIF) to maintain pluripotency of mouse embryonic stem cells (mESCs). However, in the absence of LIF, Wnt signaling is unable to maintain ESCs in the undifferentiated state. To investigate the role of canonical Wnt signaling in pluripotency and lineage specification, we expressed Wnt3a in mESCs and characterized them in growth and differentiation. We found that activated canonical Wnt signaling induced the formation of a reversible metastable primitive endoderm state in mESC. Upon subsequent differentiation, Wnt3a-stimulated mESCs gave rise to large quantities of visceral endoderm. Furthermore, we determined that the ability of canonical Wnt signaling to induce a metastable primitive endoderm state was mediated by Tbx3. Our data demonstrates a specific role for canonical Wnt signaling in promoting pluripotency while at the same time priming cells for subsequent differentiation into the primitive endoderm lineage.

Germ layer

WNT3A

Embryoid body

Histogenesis

10.1002/stem.1321

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Citations (47)

Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, <i>IDH</i>-wildtype: <i>Post Hoc</i> Analysis of the EORTC Randomized Phase III CATNON Trial

C. Mircea S. Tesileanu Marc Sanson Wolfgang Wick Alba A. Brandes Paul M. Clément

Temozolomide

Post-hoc analysis

Post hoc

Wild type

10.1158/1078-0432.22487430.v1

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Citations (0)

C. Mircea S. Tesileanu Marc Sanson Wolfgang Wick Alba A. Brandes Paul M. Clément

Temozolomide

Wild type

Post-hoc analysis

10.1158/1078-0432.22487424.v1

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MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma

Annals of Oncology (2019)

Melissa Vos Ruben Boers Anne L. M. Vriends Joachim Boers Patricia F. van Kuijk

Primary tumor

TaqMan

10.1093/annonc/mdz283.056

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Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome

Human Molecular Genetics (2010)

W. Edward Visser Sigrid Swagemakers Zeliha Özgür Rachel Schot Frans W. Verheijen

Thyroid hormone (TH) is crucial for normal brain development. TH transporters control TH homeostasis in brain as evidenced by the complex endocrine and neurological phenotype of patients with mutations in monocarboxylate transporter 8 (MCT8). We investigated the mechanisms of disease by analyzing gene expression profiles in fibroblasts from patients with MCT8 mutations. Studying MCT8 and its transcriptional context in different comprehensive spatial and temporal human brain transcriptome data sets revealed distinct region-specific MCT8 expression. Furthermore, MCT8 demonstrated a clear age-dependent decrease, suggesting its importance in early brain development. Performing comparative transcriptome analysis, we linked the genes differentially expressed (DE) in patient fibroblasts to the human brain transcriptome. DE genes in patient fibroblasts were strongly over-represented among genes highly correlated with MCT8 expression in brain. Furthermore, using the same approach we identified which genes in the classical TH signaling pathway are affected in patients. Finally, we provide evidence that the TRα2 receptor variant is closely connected to MCT8. The present study provides a molecular basis for understanding which pathways are likely affected in the brains of patients with mutations in MCT8. Our data regarding a functional relationship between MCT8 and TRα2 suggest an unanticipated role for TRα2 in the (patho)physiology of TH signaling in the brain. This study demonstrates how genome-wide expression data from patient-derived non-neuronal tissue related to the human brain transcriptome may be successfully employed to improve our understanding of neurological disease.

Human brain

Monocarboxylate transporter

10.1093/hmg/ddq337

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Citations (24)

Genomic and Nongenomic Effects of Estrogen Signaling in Human Endometrial Cells: Involvement of the Growth Factor Receptor Signaling Downstream AKT Pathway

Reproductive Sciences (2007)

S. C. J. P. Gielen Lindy A.M. Santegoets Liesbeth C. Kühne Wilfred F. J. van IJcken B. Boers-Sijmons

10.1177/1933719107306872

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Citations (16)

P267: TSC1/TSC2 mosaicism is found in ∼13% of individuals with tuberous sclerosis and is associated with a distinctive phenotypic severity