Functional Impact of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Smooth Muscle Differentiation from Stem Cells and Embryonic Arteriogenesis

Wang, Gang; Xiao, Qingzhong; Luo, Zhenling; Ye, Shu; Xu, Qingbo

doi:10.1074/jbc.m111.297028

Cited by 35 publications

(37 citation statements)

References 50 publications

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“…38,39 Previous data from our laboratory demonstrated that several signal transducers, including Nrf3-Pla2g7/Nox4-induced H 2 O 2 , histone deacetylase 7, and heterogeneous nuclear ribonucleoproteins, serve either as enhancers or inhibitors of stem cell differentiation toward the SMC lineage. [40][41][42][43][44] In the present study, we confirmed that the interaction of integrins α4/α5 and β1 with matrix protein domains of collagen IV is crucial for adventitial stem cell differentiation as identified by blocking peptides for integrin receptors. As our ex vivo data on adventitial stem cell migration into decellularized vessel wall indicated an abundance of cells that expressed smooth muscle markers, it is plausible that the infiltrated progenitor cells were driven toward SMC differentiation as a result of direct contact with matrix proteins within the vessel wall.…”

Section: Discussionsupporting

confidence: 83%

Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation

Chen

Wong

Campagnolo

et al. 2013

ATVB

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Interestingly, these resident progenitor cells have been demonstrated to differentiate into a variety of cell types, including those of the vascular lineage, in response to specific culture conditions in vitro. 13 Although seminal studies implicate the © 2013 American Heart Association, Inc. Objective-This study was designed to carry out the characterization of stem cells within the adventitia and to elucidate their functional role in the pathogenesis of vein graft atherosclerosis. Approach and Results-A mouse vein graft model was used to investigate the functional role of adventitial stem/progenitor cells on atherosclerosis. The adventitia of vein grafts underwent significant remodeling during early stages of vessel grafting and displayed markedly heterogeneous cell compositions. Immunofluorescence staining indicated a significant number of stem cell antigen-1-positive cells that were closely located to vasa vasorum. In vitro clonogenic assays demonstrated 1% to 11% of growing rates from adventitial cell cultures, most of which could be differentiated into smooth muscle cells (SMCs). These stem cell antigen-1-positive cells also displayed a potential to differentiate into adipogenic, osteogenic, or chondrogenic lineages in vitro. In light of the proatherogenic roles of SMCs in atherosclerosis, we focused on the functional roles of progenitor-SMC differentiation, in which we subsequently demonstrated that it was driven by direct interaction of the integrin/collagen IV axis. The ex vivo bioreactor system revealed the migratory capacity of stem cell antigen-1-positive progenitor cells into the vessel wall in response to stromal cell-derived factor-1. Stem cell antigen-1-positive cells that were applied to the outer layer of vein grafts showed enhanced atherosclerosis in apolipoprotein E-deficient mice, which contributed to ≈30% of neointimal SMCs. Conclusions-We demonstrate that during pathological conditions in vein grafting, the adventitia harbors stem/ progenitor cells that can actively participate in the pathogenesis of vascular disease via differentiation into SMCs.

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Section: Discussionsupporting

confidence: 83%

Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation

Chen

Wong

Campagnolo

et al. 2013

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“…33 have nicely demonstrated that RNAbinding protein HuR attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA. Moreover, our previous studies have suggested an important role for another two RBPs, hnRNPA1 11 and hnRNPA2B1, 34 in SMC differentiation. These evidence together with our observation that much less miR-34a and SirT1 3′UTR were loaded into Ago2-RISC complex upon SMC differentiation prompts us to speculate that miR-34a upregulates SirT1 during SMC differentiation through a similar mechanism as reported by Kundu et al 33 In other words, the upregulation of SirT1 by miR-34a may well be a result of RBPs, such as HuR, hnRNPA1 and hnRNPA2B1, interacting with miR-34a-binding sites and/or other elements within the 3′UTR of SirT1 to disengage it from Ago2-RISC complex during differentiation.…”

Section: S Ir T 1 a C T A 2 T A G Lnmentioning

confidence: 89%

“…Detailed protocols for mouse ESCs (mESCs) (ES-D3 cell line, CRL-1934; ATCC, Manassas, VA, USA) culture and SMC differentiation were described in our previous studies. [11][12][13][14]17,22,34,43,44 The Shef-1, 2, 3, 6, and 7 human ESC lines were obtained from the United Kingdom Stem Cell Bank (UKSCB, Hertfordshire, UK) and maintained in our Laboratory as described in our previous study. 18 Briefly, undifferentiated ESCs were dissociated into single cells and seeded onto collagen I/IV (5 μg/ml)-coated flasks or plates in differentiation medium (DM, MEM alpha medium (Gibco, Carlsbad, CA, USA) supplemented with 10% FBS, 0.05 mM 2-mercaptoethanol, 100 U/ml penicillin, and 100 μg/ml streptomycin) for 0-9 days prior to further treatment.…”

Section: S Ir T 1 a C T A 2 T A G Lnmentioning

confidence: 99%

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

Zhang

Wen

et al. 2014

Cell Death Differ

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microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevity/aging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0/G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo.

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“…[26][27][28][29][30] For instance, 2 hnRNPs (heterogeneous nuclear ribonucleoproteins), hnRNPA1 31 and hnRNPA2B1, 32 have been identified as key molecules for the regulation of VSMC differentiation from embryonic stem cells as it directly binds to promoter regions of VSMC-specific genes and transcription factors such as SRF and myocardin. hnRNPA1 also mediates its effect by recruiting Cbx3 (chromobox protein homolog gene 3), another VSMC differentiation regulatory nuclear protein.…”

Section: Vsmc Origin and Differentiationmentioning

confidence: 99%

“…hnRNPA1 also mediates its effect by recruiting Cbx3 (chromobox protein homolog gene 3), another VSMC differentiation regulatory nuclear protein. 33 Of note, knockdown of hnRNPA2B1 32 or Cbx3 33 was found to inhibit neural crest cell migration and differentiation into VSMCs, resulting in severe developmental defects of brachial arteries and reduced blood circulation in chick embryos. Similarly, a role for reactive oxygen species in regulating gene expression in stem cell-derived VSMCs has been characterized.…”

Section: Vsmc Origin and Differentiationmentioning

confidence: 99%

Differentiation and Application of Induced Pluripotent Stem Cell–Derived Vascular Smooth Muscle Cells

Maguire

Xiao

2017

ATVB

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Abstract-Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. Visual Overview-An online visual overview is available for this article.

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Functional Impact of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Smooth Muscle Differentiation from Stem Cells and Embryonic Arteriogenesis

Cited by 35 publications

References 50 publications

Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation

Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

Differentiation and Application of Induced Pluripotent Stem Cell–Derived Vascular Smooth Muscle Cells

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