A mechanoresponsive PINCH-1-Notch2 interaction regulates smooth muscle differentiation of human placental mesenchymal stem cells

Stem Cells ◽  
2021 ◽  
Vol 39 (5) ◽  
pp. 650-668
Author(s):  
Jie Su ◽  
Ling Guo ◽  
Chuanyue Wu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Muscle Differentiation ◽  
Placental Mesenchymal Stem Cells ◽  
Smooth Muscle Differentiation

scholarly journals Insulin-Like Growth Factor Binding Protein-6 Promotes the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle Independent of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Doaa Aboalola ◽  
Victor K. M. Han
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Muscle Differentiation ◽  
Insulin Like Growth Factor ◽  
Differentiation Process ◽  
Placental Mesenchymal Stem Cells

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.

scholarly journals Nrf3-Pla2g7 Interaction Plays an Essential Role in Smooth Muscle Differentiation From Stem Cells

2012 ◽  
Vol 32 (3) ◽  
pp. 730-744 ◽  
Author(s):  
Qingzhong Xiao ◽  
Anna E. Pepe ◽  
Gang Wang ◽  
Zhenling Luo ◽  
Li Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Essential Role ◽  
Muscle Differentiation ◽  
Smooth Muscle Differentiation

scholarly journals Nuclear Fusion-Independent Smooth Muscle Differentiation of Human Adipose-Derived Stem Cells Induced by a Smooth Muscle Environment

Stem Cells ◽  
2012 ◽  
Vol 30 (3) ◽  
pp. 481-490 ◽  
Author(s):  
Rong Zhang ◽  
Gregory S. Jack ◽  
Nagesh Rao ◽  
Patricia Zuk ◽  
Louis J. Ignarro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Nuclear Fusion ◽  
Muscle Differentiation ◽  
Adipose Derived Stem Cells ◽  
Smooth Muscle Differentiation

scholarly journals Single-Cell RNA-Sequencing and Metabolomics Analyses Reveal the Contribution of Perivascular Adipose Tissue Stem Cells to Vascular Remodeling

2019 ◽  
Vol 39 (10) ◽  
pp. 2049-2066 ◽  
Author(s):  
Wenduo Gu ◽  
Witold N. Nowak ◽  
Yao Xie ◽  
Alexandra Le Bras ◽  
Yanhua Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Single Cell ◽  
Rna Sequencing ◽  
Vascular Remodeling ◽  
Muscle Differentiation ◽  
Metabolic Reprogramming ◽  
Vascular Regeneration ◽  
Single Cell Rna Sequencing ◽  
Smooth Muscle Differentiation

Objective: Perivascular adipose tissue (PVAT) plays a vital role in maintaining vascular homeostasis. However, most studies ascribed the function of PVAT in vascular remodeling to adipokines secreted by the perivascular adipocytes. Whether mesenchymal stem cells exist in PVAT and play a role in vascular regeneration remain unknown. Approach and Results: Single-cell RNA-sequencing allowed direct visualization of the heterogeneous PVAT-derived mesenchymal stem cells (PV-ADSCs) at a high resolution and revealed 2 distinct subpopulations, among which one featured signaling pathways crucial for smooth muscle differentiation. Pseudotime analysis of cultured PV-ADSCs unraveled their smooth muscle differentiation trajectory. Transplantation of cultured PV-ADSCs in mouse vein graft model suggested the contribution of PV-ADSCs to vascular remodeling through smooth muscle differentiation. Mechanistically, treatment with TGF-β1 (transforming growth factor β1) and transfection of microRNA (miR)-378a-3p mimics induced a similar metabolic reprogramming of PV-ADSCs, including upregulated mitochondrial potential and altered lipid levels, such as increased cholesterol and promoted smooth muscle differentiation. Conclusions: Single-cell RNA-sequencing allows direct visualization of PV-ADSC heterogeneity at a single-cell level and uncovers 2 subpopulations with distinct signature genes and signaling pathways. The function of PVAT in vascular regeneration is partly attributed to PV-ADSCs and their differentiation towards smooth muscle lineage. Mechanistic study presents miR-378a-3p which is a potent regulator of metabolic reprogramming as a potential therapeutic target for vascular regeneration.

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