An updated view on the differentiation of stem cells into endothelial cells

Zhou, Yunyun; Yang, Feng; Chen, Ting; Wu, Yutao; Yang, Mei; Zhu, Jianhua; Zhang, Li

doi:10.1007/s11427-014-4712-4

Cited by 7 publications

(8 citation statements)

References 143 publications

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“…Finally, to shed light on the upstream signaling, which activates QKI‐5 expression in early stages of EC differentiation from iPSCs, transcription factor binding analysis on the QKI‐5 promoter has predicted a potential binding site for the transcription factor ETS1. ETS factors, and in particular ETS1 and Etv2, have been reported as key factors that regulate endothelial development . Interestingly, ETS1 is induced during EC differentiation from iPSCs in a time‐dependent manner (Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

Quaking Is a Key Regulator of Endothelial Cell Differentiation, Neovascularization, and Angiogenesis

et al. 2017

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The capability to derive endothelial cell (ECs) from induced pluripotent stem cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This study elucidates the precise role of the RNA‐binding protein Quaking isoform 5 (QKI‐5) during EC differentiation from both mouse and human iPSCs (hiPSCs) and dissects how RNA‐binding proteins can improve differentiation efficiency toward cell therapy for important vascular diseases. iPSCs represent an attractive cellular approach for regenerative medicine today as they can be used to generate patient‐specific therapeutic cells toward autologous cell therapy. In this study, using the model of iPSCs differentiation toward ECs, the QKI‐5 was found to be an important regulator of STAT3 stabilization and vascular endothelial growth factor receptor 2 (VEGFR2) activation during the EC differentiation process. QKI‐5 was induced during EC differentiation, resulting in stabilization of STAT3 expression and modulation of VEGFR2 transcriptional activation as well as VEGF secretion through direct binding to the 3′ UTR of STAT3. Importantly, mouse iPS‐ECs overexpressing QKI‐5 significantly improved angiogenesis and neovascularization and blood flow recovery in experimental hind limb ischemia. Notably, hiPSCs overexpressing QKI‐5, induced angiogenesis on Matrigel plug assays in vivo only 7 days after subcutaneous injection in SCID mice. These results highlight a clear functional benefit of QKI‐5 in neovascularization, blood flow recovery, and angiogenesis. Thus, they provide support to the growing consensus that elucidation of the molecular mechanisms underlying EC differentiation will ultimately advance stem cell regenerative therapy and eventually make the treatment of cardiovascular disease a reality. The RNA binding protein QKI‐5 is induced during EC differentiation from iPSCs. RNA binding protein QKI‐5 was induced during EC differentiation in parallel with the EC marker CD144. Immunofluorescence staining showing that QKI‐5 is localized in the nucleus and stained in parallel with CD144 in differentiated ECs (scale bar = 50 µm). stem cells 2017 Stem Cells 2017;35:952–966

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Section: Resultsmentioning

confidence: 99%

Quaking Is a Key Regulator of Endothelial Cell Differentiation, Neovascularization, and Angiogenesis

et al. 2017

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“…In terms of angiogenesis, miR-21 induces angiogenic processes and the differentiation of endothelial stem cells through targeting phosphatase and tensin homolog (PTEN). This targeting process activates AKT (protein kinase B) and extracellular regulated kinases (ERK) 1/2 signaling pathways, thereby enhancing hypoxia inducible factor-1 alpha (HIF-1α) and VEGF expression (Di Bernardini et al, 2014 ; Zhou et al, 2014 ). Although, not significantly different, the slight increase of miR-21 after HVT (1.6-fold) in the present study, is consistent with findings from Baggish et al ( 2011 ), in which circulating miR-21 was significantly up-regulated (1.9-fold) in human adults immediately following an incremental cycling step test.…”

Section: Discussionmentioning

confidence: 99%

Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

et al. 2016

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Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children.Methods:Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA.Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30′, 60′, 180′) and HVT (d3, 0′, 60′).Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

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“…Vascular endothelial cells (ECs) differentiated from PSCs have potential benefits for regenerative medicine of vascular diseases as well as in vitro disease modeling with patient-derived induced pluripotent stem cells (iPSCs), and a number of protocols for deriving ECs have been developed234. In the present work, we show the optimization of orderly endothelial cell development could be achieved by switching matrices during differentiation.…”

mentioning

confidence: 85%

Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells

Ohta

Niwa

Taniguchi

et al. 2016

Sci Rep

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Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.

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An updated view on the differentiation of stem cells into endothelial cells

Cited by 7 publications

References 143 publications

Quaking Is a Key Regulator of Endothelial Cell Differentiation, Neovascularization, and Angiogenesis

Quaking Is a Key Regulator of Endothelial Cell Differentiation, Neovascularization, and Angiogenesis

Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells

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