scholarly journals The longest telomeres: a general signature of adult stem cell compartments

2008 ◽  
Vol 22 (5) ◽  
pp. 654-667 ◽  
Author(s):  
I. Flores ◽  
A. Canela ◽  
E. Vera ◽  
A. Tejera ◽  
G. Cotsarelis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adult Stem Cell ◽  
Cell Compartments ◽  
General Signature

scholarly journals An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Marc Fiedler ◽  
Michael Graeb ◽  
Juliusz Mieszczanek ◽  
Trevor J Rutherford ◽  
Christopher M Johnson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Development ◽  
Wnt Signaling ◽  
Binding Proteins ◽  
Adult Stem Cell ◽  
Previous Evidence ◽  
Cell Compartments ◽  
Nuclear Factors ◽  
Proteomics Approach

TCF/LEF factors are ancient context-dependent enhancer-binding proteins that are activated by β-catenin following Wnt signaling. They control embryonic development and adult stem cell compartments, and their dysregulation often causes cancer. β-catenin-dependent transcription relies on the NPF motif of Pygo proteins. Here, we use a proteomics approach to discover the Chip/LDB-SSDP (ChiLS) complex as the ligand specifically binding to NPF. ChiLS also recognizes NPF motifs in other nuclear factors including Runt/RUNX2 and Drosophila ARID1, and binds to Groucho/TLE. Studies of Wnt-responsive dTCF enhancers in the Drosophila embryonic midgut indicate how these factors interact to form the Wnt enhanceosome, primed for Wnt responses by Pygo. Together with previous evidence, our study indicates that ChiLS confers context-dependence on TCF/LEF by integrating multiple inputs from lineage and signal-responsive factors, including enhanceosome switch-off by Notch. Its pivotal function in embryos and stem cells explain why its integrity is crucial in the avoidance of cancer.

scholarly journals GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 225
Author(s):  
Claire Racaud-Sultan ◽  
Nathalie Vergnolle
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Glycogen Synthase ◽  
Inflammatory Diseases ◽  
Adult Stem Cell ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Epithelial Regeneration ◽  
Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

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