V. Cesarini et al. (aug 2019)
Scientific reports 9 1 12206
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.
Aneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5,a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs,that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan,tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular,we found that affected aortas showed lower levels of all the PDE5A isoforms,compared to control aortas. Transfection of vascular SMCs (VSMCs) with NOTCH3 activated domain (NICD3) induced the expression of PDE5A1 and A3 protein isoforms,but not that of the corresponding mRNAs. VSMC stimulation with GSNO,a nitric oxide analogue or with 8-br-cGMP,but not with 8-br-cAMP,up-regulated PDE5 and NOTCH-3 protein levels,indicating a negative feedback loop to protect the arterial wall from excessive relaxation. Finally,we found that PDE5 is expressed early during human aorta development,suggesting that if loss of function mutations of PDE5 occur,they might potentially affect aortic wall development.
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产品类型:
产品号#:
04961
04965
产品名:
MegaCult™-C胶原和含细胞因子培养基
Elliott S et al. (JUL 2013)
PloS one 8 7 e68083
Epo receptors are not detectable in primary human tumor tissue samples.
Erythropoietin (Epo) is a cytokine that binds and activates an Epo receptor (EpoR) expressed on the surface of erythroid progenitor cells to promote erythropoiesis. While early studies suggested EpoR transcripts were expressed exclusively in the erythroid compartment,low-level EpoR transcripts were detected in nonhematopoietic tissues and tumor cell lines using sensitive RT-PCR methods. However due to the widespread use of nonspecific anti-EpoR antibodies there are conflicting data on EpoR protein expression. In tumor cell lines and normal human tissues examined with a specific and sensitive monoclonal antibody to human EpoR (A82),little/no EpoR protein was detected and it was not functional. In contrast,EpoR protein was reportedly detectable in a breast tumor cell line (MCF-7) and breast cancer tissues with an anti-EpoR polyclonal antibody (M-20),and functional responses to rHuEpo were reported with MCF-7 cells. In another study,a functional response was reported with the lung tumor cell line (NCI-H838) at physiological levels of rHuEpo. However,the specificity of M-20 is in question and the absence of appropriate negative controls raise questions about possible false-positive effects. Here we show that with A82,no EpoR protein was detectable in normal human and matching cancer tissues from breast,lung,colon,ovary and skin with little/no EpoR in MCF-7 and most other breast and lung tumor cell lines. We show further that M-20 provides false positive staining with tissues and it binds to a non-EpoR protein that migrates at the same size as EpoR with MCF-7 lysates. EpoR protein was detectable with NCI-H838 cells,but no rHuEpo-induced phosphorylation of AKT,STAT3,pS6RP or STAT5 was observed suggesting the EpoR was not functional. Taken together these results raise questions about the hypothesis that most tumors express high levels of functional EpoR protein.
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Human induced pluripotent stem cell-derived myotubes to model inclusion body myositis
Inclusion body myositis (IBM) is an inflammatory myopathy that displays proximal and distal muscle weakness. At the histopathological level,the muscles of IBM patients show inflammatory infiltrates,rimmed vacuoles and mitochondrial changes. The etiology of IBM remains unknown,and there is a lack of validated disease models,biomarkers and effective treatments. To contribute to unveil disease underpins we developed a cell model based on myotubes derived from induced pluripotent stem cells (iPSC-myotubes) from IBM patients and compared the molecular phenotype vs. age and sex-paired controls (n?=?3 IBM and 4 CTL). We evaluated protein histological findings and the gene expression profile by mRNA-seq,alongside functional analysis of inflammation,degeneration and mitochondrial function. Briefly,IBM iPSC-myotubes replicated relevant muscle histopathology features of IBM,including aberrant expression of HLA,TDP-43 and COX markers. mRNA seq analysis identified 1007 differentially expressed genes (DEGs) (p-value adj?0.01; 789 upregulated and 218 downregulated),associated with myopathy,muscle structure and developmental changes. Among these,1 DEG was related to inflammation,28 to autophagy and 28 to mitochondria. At the functional level,inflammation was similar between the IBM and CTL groups under basal conditions (mean cytokine expression in IBM 4.6?±?1.4 vs. 6.7?±?3.4 in CTL),but increased in IBM iPSC-myotubes after lipopolysaccharide treatment (72.5?±?21.8 in IBM vs. 13.0?±?6.7 in CTL). Additionally,autophagy was disturbed,with 40.14% reduction in autophagy mediators. Mitochondrial dysfunction was strongly manifested,showing a conserved respiratory profile and antioxidant capacity,but a 56.33% lower cytochrome c oxidase/citrate synthase ratio and a 66.59% increase in lactate secretion. Overall,these findings support patient-derived iPSC-myotubes as a relevant model for IBM,reflecting the main muscle hallmarks,including inflammation,autophagy dysfunction and mitochondrial alterations at transcriptomic,protein and functional levels.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40478-025-01933-0. Transcriptomic and functional validation of iPSC-derived myotubes from IBM patients revealed that they displayed the main hallmarks of the disease.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40478-025-01933-0.
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产品类型:
产品号#:
85850
85857
产品名:
mTeSR™1
mTeSR™1
(Mar 2024)
Nature Cell Biology 26 3
Distinct pathways drive anterior hypoblast specification in the implanting human embryo
Development requires coordinated interactions between the epiblast,which generates the embryo proper; the trophectoderm,which generates the placenta; and the hypoblast,which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent,as in the mouse. However,while BMP inhibits anterior signalling centre specification in the mouse,it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally,we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies. Weatherbee,Weberling,Gantner et al. find contrasting requirements for BMP in the anterior signalling centre and pre-implantation epiblast between mice and humans. They further find that NOTCH may be indispensable for human epiblast survival.
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产品类型:
产品号#:
100-0276
100-1130
85850
85857
产品名:
mTeSR™ Plus
mTeSR™ Plus
mTeSR™1
mTeSR™1
(Jan 2025)
PLOS ONE 20 1
The MIR-NAT MAPT-AS1 does not regulate Tau expression in human neurons
The MAPT gene encodes Tau protein,a member of the large family of microtubule-associated proteins. Tau forms large insoluble aggregates that are toxic to neurons in several neurological disorders,and neurofibrillary Tau tangles represent a key pathological hallmark of Alzheimer’s disease (AD) and other tauopathies. Lowering Tau expression levels constitutes a potential treatment for AD but the mechanisms that regulate Tau expression at the transcriptional or translational level are not well understood. Natural antisense transcripts (NATs) are a particular class of long non-coding RNAs (lncRNAs) that can regulate expression of their overlapping protein-coding genes at the epigenetic,transcriptional,or translational level. We and others identified a long non-coding RNA associated with the MAPT gene,named MAPT antisense 1 (MAPT-AS1). We confirmed that MAPT-AS1 is expressed in neurons in human post mortem brain tissue. To study the role of MAPT-AS1 on MAPT expression regulation,we modulated the expression of this lncRNA in human neuroblastoma cell lines and in human induced pluripotent stem cell (iPSC) derived neurons. In contrast to previous reports,we observed no changes on MAPT mRNA or Tau protein levels upon modulation of MAPT-AS1 levels in these cellular models. Our data suggest that MAPT-AS1 does not regulate Tau expression levels in human neurons in vitro. Thus,MAPT-AS1 does not represent a valuable therapeutic target to lower Tau expression in patients affected by tauopathies including AD.
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产品类型:
产品号#:
85850
85857
产品名:
mTeSR™1
mTeSR™1
H. Shin et al. (Aug 2025)
PLOS One 20 8
Skin irritation testing using human iPSCs derived 3D skin equivalent model
Artificial skin models have emerged as valuable tools for evaluating cosmetic ingredients and developing treatments for skin regeneration. Among them,3D skin equivalent models (SKEs) using human primary skin cells are widely utilized and supported by standardized testing guidelines. However,primary cells face limitations such as restricted donor availability and challenges in conducting genotype-specific studies. To overcome these issues,recent approaches have focused on differentiating skin cells from human-induced pluripotent stem cells (hiPSCs). In this study,we developed a protocol to differentiate high-purity skin cells,such as fibroblasts (hFIBROs) and keratinocytes (hKERAs),from hiPSCs. To construct the hiPSC-derived SKE (hiPSC-SKE),a dermis was first formed by culturing a collagen and hFIBROs mixture within an insert. Subsequently,hKERAs were seeded onto the dermis,and keratinization was induced under air-liquid culture conditions to establish an epidermis. Histological analysis with hematoxylin and eosin staining confirmed that the hiPSC-SKE recapitulated the layered architecture of native human skin and expressed appropriate epidermal and dermal markers. Moreover,exposure to Triton X-100,a known skin irritant,led to marked epidermal damage and significantly reduced cell viability,validating the model’s functional responsiveness. These findings indicate that the hiPSC-SKE model represents a promising alternative for various skin-related applications,including the replacement of animal testing.
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产品类型:
产品号#:
85850
85857
产品名:
mTeSR™1
mTeSR™1
Sorio C et al. (JAN 2011)
PloS one 6 7 e22212
Defective CFTR expression and function are detectable in blood monocytes: development of a new blood test for cystic fibrosis.
BACKGROUND Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION Western blot,PCR,immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging,using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated,cell membrane-localized CFTR was detected in non-CF monocytes,being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and,to a lesser extent,obligate CFTR heterozygous carriers (HTZ: 15 subjects),but it failed in monocytes from CF patients (44 subjects). We propose an index,which values in CF patients are significantly (ptextless0.001) lower than in the other two groups. Nasal Potential Difference,measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93,95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials.
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产品类型:
产品号#:
73602
73604
产品名:
8-Bromo-cAMP
8-Bromo-cAMP
A. Wardaszka et al. (Jul 2025)
International Journal of Molecular Sciences 26 14
Selection of Stable Reference Genes for Gene Expression Studies in Activated and Non-Activated PBMCs Under Normoxic and Hypoxic Conditions
Immunotherapy has emerged as a key modality in cancer treatment,yet its effectiveness varies significantly among patients,often due to the metabolic stress imposed by the tumor microenvironment. Hypoxia,a major factor in the tumor microenvironment,results from the high metabolic rate of tumor cells and inadequate vascularization,impairing immune cells’ function and potentially influencing gene expression profiles. Despite the widespread use of quantitative real-time PCR in immunological studies,to the best of our knowledge,data on reference gene stability in human peripheral blood mononuclear cells under hypoxic conditions is limited. In our study,we assessed the expression stability of commonly used reference genes ( S18,HPRT,IPO8,RPL13A,SDHA,PPIA,and UBE2D2 ) in both non-stimulated and CD3/CD28-activated peripheral blood mononuclear cells cultured under normoxic,hypoxic (1% O 2 ),and chemically induced hypoxic conditions for 24 h. Analysis using four different algorithms—delta Ct,geNorm,NormFinder,and BestKeeper—identified RPL13A,S18,and SDHA as the most suitable reference genes for human peripheral blood mononuclear cells under hypoxic conditions. In contrast,IPO8 and PPIA were found to be the least suitable housekeeping genes. The study provides essential insights into the stability of reference genes in peripheral blood mononuclear cells under hypoxic conditions,a critical but understudied aspect of immunological research. Given the significant impact of hypoxia on T cell metabolism and function in the tumor microenvironment,selecting reliable reference genes is crucial for accurate gene expression analysis. Our findings will be valuable for future studies investigating hypoxia-driven metabolic reprogramming in immune cells,ultimately contributing to a better understanding of T cell responses in cancer immunotherapy.
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产品类型:
产品号#:
100-0784
10971
10991
85450
85460
产品名:
ImmunoCult™ 人CD3/CD28 T细胞激活剂
ImmunoCult™ 人CD3/CD28 T细胞激活剂
ImmunoCult™ 人CD3/CD28 T细胞激活剂
SepMate™-50 (IVD)
SepMate™-50 (IVD)
G. A. Rouleau et al. (Mar 2026)
Neurology: Genetics 12 2
Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C > A for Exon 27 Splicing and Axonal Transport of SFPQ
Background and Objectives: Recent studies have identified variants in the kinesin family member 5A (KIF5A) gene that predispose to amyotrophic lateral sclerosis (ALS). These ALS-linked KIF5A variants lead to the exclusion of exon 27,resulting in the production of a mutated protein with an altered C-terminal region (KIF5A ΔExon27). Through whole genome sequencing,we identified a novel KIF5A intronic variant,rs1057522322 (c.2993-6C > A; chr12:57582596C > A,GRCh38.p14),in a family segregating ALS. Our goal is to investigate the effect of this variant on exon 27 splicing and to assess its functional consequences on KIF5A-mediated cargo transport. Methods: Induced pluripotent stem cells (iPSCs) were generated from siblings with and without the c.2993-6C > A variant. RT-PCR was performed on RNA extracted from iPSC-derived neurons to assess exon 27 splicing. Functional studies were conducted on iPSC-derived motor neurons (MNs). Results: RT-PCR confirmed that the c.2993-6C > A variant induced exon 27 skipping in KIF5A. Immunofluorescent staining showed that KIF5A ΔExon27 abolished the axonal interaction with splicing factor proline- and glutamine-rich,a cargo specifically transported by KIF5A. Under stress conditions,MNs carrying the c.2993-6C > A variant exhibited TDP-43 proteinopathy. Discussion: KIF5A intronic variant c.2993-6C > A could be a risk factor for ALS. KIF5A ΔExon27 impairs KIF5A-mediated cargo transport and contributes to ALS pathogenesis in a TDP-43–dependent manner.
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产品类型:
产品号#:
05833
05835
05839
08581
08582
18000
19669
19669RF
20104
20124
20164
85850
85857
产品名:
STEMdiff™神经前体细胞培养基
STEMdiff™ 神经诱导培养基
STEMdiff™ 神经诱导培养基
STEMdiff™SMADi神经诱导试剂盒
STEMdiff™SMADi神经诱导试剂盒,2套
EasySep™磁极
EasySep™ Direct人单核细胞分选试剂盒
RoboSep™ Direct人单核细胞分选试剂盒
RoboSep™ 缓冲液
RoboSep™ 缓冲液 (5X浓缩液)
RoboSep™ 缓冲液 2
mTeSR™1
mTeSR™1
Perez JE et al. (FEB 2017)
Nanotechnology 28 5 55703
Mesenchymal stem cells cultured on magnetic nanowire substrates.
Stem cells have been shown to respond to extracellular mechanical stimuli by regulating their fate through the activation of specific signaling pathways. In this work,an array of iron nanowires (NWs) aligned perpendicularly to the surface was fabricated by pulsed electrodepositon in porous alumina templates followed by a partial removal of the alumina to reveal 2-3 μm of the NWs. This resulted in alumina substrates with densely arranged NWs of 33 nm in diameter separated by 100 nm. The substrates were characterized by scanning electron microscopy (SEM) energy dispersive x-ray analysis and vibrating sample magnetometer. The NW array was then used as a platform for the culture of human mesenchymal stem cells (hMSCs). The cells were stained for the cell nucleus and actin filaments,as well as immuno-stained for the focal adhesion protein vinculin,and then observed by fluorescence microscopy in order to characterize their spreading behavior. Calcein AM/ethidium homodimer-1 staining allowed the determination of cell viability. The interface between the cells and the NWs was studied using SEM. Results showed that hMSCs underwent a re-organization of actin filaments that translated into a change from an elongated to a spherical cell shape. Actin filaments and vinculin accumulated in bundles,suggesting the attachment and formation of focal adhesion points of the cells on the NWs. Though the overall number of cells attached on the NWs was lower compared to the control,the attached cells maintained a high viability (>90%) for up to 6 d. Analysis of the interface between the NWs and the cells confirmed the re-organization of F-actin and revealed the adhesion points of the cells on the NWs. Additionally,a net of filopodia surrounded each cell,suggesting the probing of the array to find additional adhesion points. The cells maintained their round shape for up to 6 d of culture. Overall,the NW array is a promising nanostructured platform for studying and influencing hMSCs differentiation.
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产品类型:
产品号#:
70022
70071
产品名:
Wu X et al. (JAN 2018)
Cell 172 3 423--438.e25
Intrinsic Immunity Shapes Viral Resistance of Stem Cells.
Stem cells are highly resistant to viral infection compared to their differentiated progeny; however,the mechanism is mysterious. Here,we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that,conserved across species,stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic,as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner,and many ISGs decrease upon differentiation,at which time cells become IFN responsive,allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly,we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.
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产品类型:
产品号#:
02691
04434
04444
05110
05711
05712
05872
05873
18056
18056RF
72052
72054
72302
72304
72307
72308
70039
70039.1
70039.2
70039.3
70039.4
70039.5
70039.6
60062
60062BT
60062FI
60062FI.1
60062PE
60062PE.1
60045
60045AZ
60045AZ.1
60045BT
60045FI
60045FI.1
600
产品名:
StemSpan™ CD34+扩增添加物 (10X)
MethoCult™ H4434 Classic
MethoCult™ H4434 Classic
STEMdiff™定型内胚层检测试剂盒
NeuroCult™ SM1 神经添加物
CHIR99021
CHIR99021
Y-27632(二盐酸盐)
Y-27632(二盐酸盐)
Y-27632(二盐酸盐)
Y-27632(二盐酸盐)
抗人SSEA-4抗体,克隆号MC-813-70,生物素
抗人SSEA-4抗体,克隆号MC-813-70,FITC
抗人SSEA-4抗体, 克隆号MC-813-70,FITC
抗人SSEA-4抗体,克隆号MC-813-70,PE
抗人SSEA-4抗体,克隆号MC-813-70,PE
抗人CD90抗体,克隆5E10
抗人CD90抗体,克隆5E10,APC
抗人CD90抗体,克隆5E10,APC
抗人CD90抗体,克隆5E10,Biotin
抗人CD90抗体,克隆5E10,FITC
抗人CD90抗体,克隆5E10,FITC
Bhattacharyya S and Khanduja KL (APR 2010)
Acta biochimica et biophysica Sinica 42 4 237--42
New hope in the horizon: cancer stem cells.
The major goal of researchers and oncologists is to develop promising ground for novel therapeutic strategies to prevent recurrence or relapse of cancer. Recent evidences suggest that a subset of cells called cancer stem cells (CSCs) are present within the tumor mass which possess tumorigenic capacity and may be responsible for propagation,relapse,and metastatic dissemination. These cells have certain stem cell-like properties,e.g. quiescence,selfrenewal,asymmetric division,and multidrug resistance which allow them to drive tumor growth and evade conventional therapies. A number of markers and assays have been designed to isolate and characterize the CSC population from the bulk tumor. The objective now is to selectively target the CSCs in order to eliminate the tumor from root,overcoming the emergence of clones capable of evading traditional therapy. This approach may help in increasing the overall disease-free survival in some cancers.
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