Ethanol Effects on Transcription Factor Network Regulating Stem Cell Differentiation

Author(s):  
Rajanikanth Vadigepalli ◽  
Joshua Ogony ◽  
Helen Anni
2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Laura Hyväri ◽  
Sari Vanhatupa ◽  
Heidi T. Halonen ◽  
Minna Kääriäinen ◽  
Susanna Miettinen

Previous studies have demonstrated that myocardin-related transcription factor A (MRTF-A) generates a link between the dynamics of the actin cytoskeleton and gene expression with its coregulator, serum response factor (SRF). MRTF-A has also been suggested as a regulator of stem cell differentiation. However, the role of MRTF-A in human mesenchymal stem cell differentiation remains understudied. We aimed to elucidate whether MRTF-A is a potential regulator of human adipose stem cell (hASC) differentiation towards adipogenic and osteogenic lineages. To study the role of MRTF-A activity in the differentiation process, hASCs were cultured in adipogenic and osteogenic media supplemented with inhibitor molecules CCG-1423 or CCG-100602 that have been shown to block the expression of MRTF-A/SRF-activated genes. Our results of image-based quantification of Oil Red O stained lipid droplets and perilipin 1 staining denote that MRTF-A inhibition enhanced the adipogenic differentiation. On the contrary, MRTF-A inhibition led to diminished activity of an early osteogenic marker alkaline phosphatase, and export of extracellular matrix (ECM) proteins collagen type I and osteopontin. Also, quantitative Alizarin Red staining representing ECM mineralization was significantly decreased under MRTF-A inhibition. Image-based analysis of Phalloidin staining revealed that MRTF-A inhibition reduced the F-actin formation and parallel orientation of the actin filaments. Additionally, MRTF-A inhibition affected the protein amounts of α-smooth muscle actin (α-SMA), myosin light chain (MLC), and phosphorylated MLC suggesting that MRTF-A would regulate differentiation through SRF activity. Our results strongly indicate that MRTF-A is an important regulator of the balance between osteogenesis and adipogenesis of hASCs through its role in mediating the cytoskeletal dynamics. These results provide MRTF-A as a new interesting target for guiding the stem cell differentiation in tissue engineering applications for regenerative medicine.


2019 ◽  
Vol 12 (570) ◽  
pp. eaax0926
Author(s):  
Annalisa M. VanHook

Lysosomal signaling enables stem cell differentiation by sequestering the transcription factor Tfe3 in the cytoplasm.


Author(s):  
Priyanka Sharma ◽  
Chandramani B. More ◽  
Avinash K. Seth

Aim: Hairy/enhancer of split homolog-1 (Hes1) is a transcription factor with bHLH domains and participates in controlling proliferation and differentiation of various stem cell progenitors. The study aims to analyze pathways and genes up regulated and co-expressed with Hes1 to examine their linkage with adipocyte stem cell differentiation in obesity. Methodology: In this in silico analysis, Gene Expression Omnibus Dataset GDS5056 was used to shortlist 23 genes differentially up regulated and co-expressed along with Hes1 during adipocyte stem cell differentiation in obese patients. Then, these genes along with their interactor genes were submitted to Reactome pathway analysis database and were statistically analyzed. Results: Total 12 enriched pathways were obtained which majorly belonged to two categories: neuronal cell differentiation and signaling; and inflammatory response. Since Hes1 is known to regulate such pathways as a master transcription factor and repressor, its level of expression determines the result as proliferation or differentiation. Thus, these in silico findings may help in designing future experiments to determine role of Hes1 in deciding fate of adipocyte differentiation or proliferation in obesity.


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