scholarly journals Senescent Growth Arrest in Mesenchymal Stem Cells Is Bypassed by Wip1-Mediated Downregulation of Intrinsic Stress Signaling Pathways

Stem Cells ◽  
2009 ◽  
Vol 27 (8) ◽  
pp. 1963-1975 ◽  
Author(s):  
Ji-Seon Lee ◽  
Mi-Ok Lee ◽  
Bo-Hyun Moon ◽  
Sung Han Shim ◽  
Albert J. Fornace ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Growth Arrest ◽  
Intrinsic Stress ◽  
Stress Signaling

scholarly journals Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Jett B. Murray ◽  
LeeAnn A. Hold ◽  
Jeff M. Courtright ◽  
Anne M. Carper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Cell Alignment ◽  
Limited Information ◽  
Akt Inhibitor ◽  
Tenogenic Differentiation

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

scholarly journals Mesenchymal stem cells regulate maintenance of neural stem cells through VEGFR2 and Notch signaling pathways

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S59-S59
Author(s):  
Zhifeng Deng ◽  
Zhumin Liu ◽  
Wei Tu ◽  
Yang Wang ◽  
Yuanlei Lou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathways

scholarly journals Adenosine Triphosphate Prevents Serum Deprivation-Induced Apoptosis in Human Mesenchymal Stem Cells via Activation of the MAPK Signaling Pathways

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Jessica L. Berlier ◽  
Sabrina Rigutto ◽  
Antoine Dalla Valle ◽  
Jessica Lechanteur ◽  
Muhammad S. Soyfoo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Adenosine Triphosphate ◽  
Human Mesenchymal Stem Cells ◽  
Mapk Signaling ◽  
Serum Deprivation ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

Abstract 13695: Paracrine-mediated Rejuvenation of Aged Mesenchymal Stem Cells Involves Broad Transcriptional Modulation of Angiogenic Factors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
George Hung ◽  
Andreas S Barth ◽  
Peter V Johnston ◽  
Gary Gerstenblith
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Tissue Repair ◽  
Target Enrichment ◽  
Aged Patients ◽  
Vegf Signaling ◽  
Marrow Mesenchymal Stem Cells ◽  
C57bl Mice ◽  
Transcriptional Modulation

Introduction: Angiogenesis induced by bone marrow mesenchymal stem cells (MSCs) obtained from aged mice is inferior to those obtained from young mice, but is improved following exposure to conditioned media (CM) from young MSCs. To define alterations in gene expression and signaling pathways underlying the observed angiogenic improvement, we characterized differences in cellular mRNA expression between “non-rejuvenated” and “rejuvenated” (exposed to CM from young MSCs) old MSCs. Methods: Replicates of 105 MSCs isolated from old (18-24 months) C57BL mice (n=6) were cultured separately, or in co-culture with MSCs from young (4-6 weeks, n=6) mice using 0.4μm Transwell plates that allow transfer of soluble factors, but not of cells. After 7d in culture, mRNA from old and rejuvenated MSCs was isolated and sequenced. Analysis was performed using open source Galaxy pipeline. Transcription factor (TF) and miRNA target enrichment analyses were performed using ChEA3 and MIENTURNET. Results: Of the 529 unique transcripts involved in angiogenesis (GO-ID 0001525), 98 differentially expressed transcripts (Bonferroni p < 0.0001) were identified. The rejuvenated MSCs showed significantly increased expression of 39 genes. The majority of these involved canonical angiogenic pathways and/or regulation of VEGF: JAK1, LOXL2, KLF4, BMP4, and ADM. Top enriched TFs and miRNAs included EPAS1 and miR-20a, respectively, both directly involved in VEGF signaling, along with SOX18, SNAI1, SOX7, miR-126a, and miR-499 (FDR < 0.05), all of which are known to promote either angiogenesis and/or stemness. Conclusions: Improved angiogenesis by old MSCs exposed to CM from young MSCs is accompanied by significant modulation of angiogenic mediators, crucial in both VEGF and non-VEGF signaling pathways. These changes suggest targets for transcriptional modification to improve angiogenesis and tissue repair in aged patients.

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