Extracellular Matrix and Integrins in Embryonic Stem Cell Differentiation

Wang, Han; Luo, Xie; Leighton, Jake

doi:10.4137/bci.s30377

Cited by 40 publications

(26 citation statements)

References 95 publications

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“…Integrins are a large family of heterodimeric cell-surface adhesion receptors which mediate cell-matrix and cell-cell interactions (Gasparski & Beningo, 2015;Wang, Luo, & Leighton, 2015). They are generally composed of noncovalently linked α and β subunits.…”

Section: Introductionmentioning

confidence: 99%

Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia

Lian

Zhang

et al. 2018

Journal Cellular Physiology

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Previous studies have been indicated that integrin α2 (ITGA2) may be important in cell migration, invasion, survival, and angiogenesis. However, the correlation between ITGA2 expression and acute myeloid leukemia (AML) is still unclear. Real-time quantitative polymerase chain reaction was carried out to analyze ITGA2 messenger RNA level. Methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR were performed to detect the methylation of ITGA2 promoter. ITGA2 expression was significantly upregulated in 134 de novo AML patients compared with 33 controls (p = 0.007). ITGA2 group had markedly lower complete remission (CR) rate than ITGA2 group (p = 0.011). Furthermore, the overall survival in ITGA2 patients was significantly shorter than ITGA2 patients throughout AML cohort, non-acute promyelocytic leukemia (APL) and cytogenetic normal-AML (p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole-cohort AML patients (p = 0.018) and non-APL AML patients (p = 0.021). Besides, ITGA2 expression level was significantly decreased in AML patients after CR (p = 0.011), and was returned at the time of relapse phase (p = 0.021). Moreover, unmethylated ITGA2 promoter was identified in normal controls, leukemia cell lines, and primary leukemia cells with low or high ITGA2 expression. In conclusions, methylation-independent ITGA2 overexpression is associated with poor prognosis in AML.

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Section: Introductionmentioning

confidence: 99%

Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia

Lian

Zhang

et al. 2018

Journal Cellular Physiology

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“…Specialized microenvironments (niches) are suggested to provide the multiple extracellular signals necessary to maintain the stemness of hPSCs 7 – 10 . Previous studies have indicated that niche-dependent extracellular matrices (ECMs) facilitate the self-renewal and pluripotency of PSCs 11 , 12 , with growth factors (such as basic fibroblast growth factor, bFGF, and epidermal growth factor, EGF) regulating their growth and survival 13 . Recent studies also suggest that niche-providing cytokines are possibly involved in the maintenance of PSCs 14 .…”

Section: Introductionmentioning

confidence: 99%

Protein profiling identified key chemokines that regulate the maintenance of human pluripotent stem cells

Jiang

et al. 2017

Sci Rep

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Microenvironment (or niche)-providing chemokines regulate many important biological functions of tissue-specific stem cells. However, to what extent chemokines influence human pluripotent stem cells (hPSCs) is not yet completely understood. In this study, we applied protein array to screen chemokines found within the cytokine pool in the culture supernatant of hPSCs. Our results showed that chemokines were the predominant supernatant components, and came from three sources: hPSCs, feeder cells, and culture media. Chemotaxis analysis of IL-8, SDF-1α, and IP-10 suggested that chemokines function as uniform chemoattractants to mediate in vitro migration of the hPSCs. Chemokines mediate both differentiated and undifferentiated states of hPSCs. However, balanced chemokine signaling tends to enhance their stemness in vitro. These results indicate that chemokines secreted from both stem cells and feeder cells are essential to mobilize hPSCs and maintain their stemness.

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“…On the other hand, integrins have also been demonstrated to play a role in stem cell differentiation. 46 The Notch signaling pathway has been shown to promote vascular maturation, 47 even by inducing integrin-mediated cell adhesion to the endothelial basement membrane. 48 We further tested the effect of LXW7 on the expression of immature and mature endothelial markers and Notch signaling pathway genes.…”

Section: Resultsmentioning

confidence: 99%

Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration

et al. 2017

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Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and structural stability. One-bead one-compound (OBOC) combinatorial technology is an ultrahigh throughput chemical library synthesis and screening method suitable for ligand discovery against a wide range of biological targets, such as integrins. In this study, using primary human EPCs/ECs as living probes, we identified an αvβ3 integrin ligand LXW7 discovered by OBOC combinatorial technology as a potent and specific EPC/EC targeting ligand. LXW7 overcomes the major barriers of other functional biomolecules that have previously been used to improve vascularization for tissue regeneration and possesses optimal stability, EPC/EC specificity, and functionality. LXW7 is a disulfide cyclic octa-peptide (cGRGDdvc) containing unnatural amino acids flanking both sides of the main functional motif; therefore it will be more resistant to proteolysis and more stable in vivo compared to linear peptides and peptides consisting of only natural amino acids. Compared with the conventional αvβ3 integrin ligand GRGD peptide, LXW7 showed stronger binding affinity to primary EPCs/ECs but weaker binding to platelets and no binding to THP-1 monocytes. In addition, ECs bound to the LXW7 treated culture surface exhibited enhanced biological functions such as proliferation, likely due to increased phosphorylation of VEGF receptor 2 (VEGF-R2) and activation of mitogen-activated protein kinase (MAPK) ERK1/2. Surface modification of electrospun microfibrous PLLA/PCL biomaterial scaffolds with LXW7 via Click chemistry resulted in significantly improved endothelial coverage. LXW7 and its derivatives hold great promise for EPC/EC recruitment and delivery and can be widely applied to functionalize various biological and medical materials to improve endothelialization and vascularization for tissue regeneration applications.

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Extracellular Matrix and Integrins in Embryonic Stem Cell Differentiation

Cited by 40 publications

References 95 publications

Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia

Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia

Protein profiling identified key chemokines that regulate the maintenance of human pluripotent stem cells

Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration

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