Contact Us / Request a Quote Download Manuals
Advanced Cell Diagnostics Advanced Cell Diagnostics

Search form

Please sign in
  • Log In
  • Register
  • How to Order
  • What to Buy
0 My Cart
X

You have no items in your shopping cart.

Menu
X
  • Products +
    RNAscope™/BaseScope™/ miRNAscope™
    +
    • Assay Selection Guide
    Target Probes
    +
    • All About Probes
    • Catalog Probes
    • Probe Sets
    • New Probe Request
    Manual Assays
    +
    RNAscope™ Chromogenic
    • Overview
    • RNAscope™ 2.5 HD Assay-Brown
    • RNAscope™ 2.5 HD Assay-Red
    • RNAscope™ 2.5 HD Duplex Assay
    RNAscope™ Multiplex Fluorescent
    • Overview
    • RNAscope™ HiPlex v2 Assay
    • RNAscope™ Multiplex Fluorescent V2
    BaseScope™
    • Overview
    • BaseScope™ Assay Red
    • BaseScope™ Duplex Assay
    miRNAscope™
    • Overview
    • miRNAscope™ Assay red
    • RNAscope™ Plus smRNA-RNA Assay
    DNAscope™
    • Overview
    • DNAscope™ Duplex Assay
    Automated Assays
    +
    For Lunaphore COMET™
    • RNAscope™ HiPlex Pro for COMET™
    For Leica systems
    • Overview
    • RNAscope™ 2.5 LS Assay-Brown
    • RNAscope™ 2.5 LS Assay-Red
    • RNAscope™ 2.5 LS Duplex Assay
    • RNAscope™ Multiomic LS Assay
    • RNAscope™ 2.5 LS Fluorescent Multiplex Assay
    • RNAscope™ 2.5 LSx Reagent Kit-BROWN
    • RNAscope™ 2.5 LSx Reagent Kit-RED
    • BaseScope™ LS Reagent Kit – RED
    • miRNAscope LS Reagent Kit Red
    • RNAscope™ Plus smRNA-RNA LS Assay
    Roche DISCOVERY ULTRA system
    • Overview
    • RNAscope™ VS Universal HRP
    • RNAscope™ VS Universal AP
    • RNAscope™ VS Duplex Assay
    • BaseScope™ VS Reagent Kit – RED
    RNA-Protein Co-Detection Assay
    +
    • RNAscope HiPlex-IMC™ Co-Detection
    • Integrated Codetection Assay
    • Sequential RNA Protein Detection
    Software
    +
    • Overview
    • Aperio RNA ISH Algorithm
    • HALO® image analysis platform
    Controls & Accessories
    +
    • RNAscope™
    • BaseScope™
    • miRNAscope™
    • Accessories
    How to Order
    +
    • Ordering Instructions
    • What to Buy
  • Services +
    Professional Assay Services
    +
    • Our Services
    • Multiomic Services
    • Biomarker Assay Development
    • Cell & Gene Therapy Services
    • Clinical Assay Development
    • Tissue Bank & Sample Procurement
    • Image Analysis
    Benefits
    +
    • Your Benefits
    • Certified Providers
    How to Order
    +
    • Ordering Process
    • Contact Services
  • Areas of Research +
    Most Popular
    +
    • COVID-19 Coronavirus
    • Single Cell Analysis
    • Whole-Mount
    • Anatomic Pathology Panels
    • Neuroscience
    • Inflammation
    • Gene Therapy/AAV
    • Stem Cell
    • Immuno-oncology
    • Liver Research
    • Cardiovascular & Skeletal Muscle Research
    Cell & Gene Therapy
    +
    • Gene Therapy
    • Gene Therapy/AAV
    • siRNA/ASO
    • Cell Therapy
    Cancer
    +
    • Breast Cancer
    • EGFRvIII Splice Variant
    • HPV Related Cancer
    • Immuno-oncology
    • Lung Cancer
    • PDx
    • Prostate Cancer
    • Point Mutation
    • CDR3 for TCR
    Viral
    +
    • COVID-19 Coronavirus
    • HIV & SIV
    • Infectious Disease
    • Zika Virus
    Pathways
    +
    • AKT
    • JAK STAT
    • WNT B-Catenin
    Neuroscience
    +
    Neuroscience
    • Neural Development
    • Neuronal Cell Types
    • Learning and Memory
    • G-protein-coupled Receptors & Ion Channels
    • Post-mortem Brain Tissue
    Other
    +
    • Circular RNA
    • Gene Fusions
    • HT Transcript Validation
    • Long Non-coding RNA
    • RNAseq Validation
    • Single Cell Analysis
    • Splice Variant
    • miRNA
    RNA & Protein
    +
    • Antibody Challenges
    • Dual ISH + IHC Methods
    • No Antibodies
    • RNA & Protein Analysis
    Customer Innovations
    +
    • Dual RNA+DNA ISH
    • Very old FFPE ISH
    • Wholemount ISH
    Animal Models
    +
    • Any Species
    • Mouse Model
    • Preclincal Safety
  • Technology +
    Overview
    +
    • How it Works
    • Data Image Gallery
    • Technology Video
    • Webinars
    RNA Detection
    +
    • Why RNA?
    • RNA ISH and IHC
    Pretreatment Options
    +
    • RNAscope™ Pretreatment
    • PretreatPro™
    Spotlights
    +
    • Researchers Spotlights
    • RNA & DNA
    • WISH
    • FFPE
    • Testimonials
    Publications, Guides & Posters
    +
    • Search publications
    • RNAscope™ Reference Guide
    • RNAscope™ Data Analysis Guide
    • Download RNAscope™ Posters
  • Support +
    Overview
    +
    • Get Started
    • How to Order
    • Distributors
    • Contact Support
    Troubleshooting
    +
    • Troubleshooting Guide
    • FAQs
    • User Manuals, SDS and Product Inserts
    • Documents and Downloads
    Imaging Resource
    +
    • Image Analysis
    • Image Registration Software
    • QuPath
    • HALO® image analysis platform
    Learn More
    +
    • Webinars
    • Training Videos
  • Partners +
    Partners
    +
    • Overview
    Partners Directory
    +
    Automation Partners
    • Leica Biosystem
    • Roche Diagnostics
    Workflow Partners
    • NanoString
    Software Partners
    • indica labs
    Become a Partner
    +
    • Learn How
  • Diagnostics +
    Diagnostics
    +
    • Diagnostics
    • Literature
    • Diagnostics ASR Probes
    • Diagnostics CE-IVD Probes
    • Diagnostics CE-IVD Detection
    • Companion Diagnostics
  • Image Calendar +
    Image Calendar
    +
    • Image Contest
    • Data Image Gallery
Search

Probes for INS

ACD can configure probes for the various manual and automated assays for INS for RNAscope Assay, or for Basescope Assay compatible for your species of interest.

  • Probes for INS (0)
  • Kits & Accessories (0)
  • Support & Documents (0)
  • Publications (26)
  • Image gallery (0)
Refine Probe List

Content for comparison

Gene

  • TBD (1413) Apply TBD filter
  • Lgr5 (151) Apply Lgr5 filter
  • SARS-CoV-2 (136) Apply SARS-CoV-2 filter
  • Gad1 (90) Apply Gad1 filter
  • vGlut2 (80) Apply vGlut2 filter
  • HPV E6/E7 (78) Apply HPV E6/E7 filter
  • Slc17a6 (77) Apply Slc17a6 filter
  • Axin2 (74) Apply Axin2 filter
  • SLC32A1 (74) Apply SLC32A1 filter
  • FOS (73) Apply FOS filter
  • Sst (65) Apply Sst filter
  • TH (63) Apply TH filter
  • VGAT (58) Apply VGAT filter
  • Gad2 (54) Apply Gad2 filter
  • tdTomato (54) Apply tdTomato filter
  • DRD2 (53) Apply DRD2 filter
  • Slc17a7 (52) Apply Slc17a7 filter
  • GLI1 (51) Apply GLI1 filter
  • PVALB (47) Apply PVALB filter
  • egfp (46) Apply egfp filter
  • ZIKV (46) Apply ZIKV filter
  • DRD1 (42) Apply DRD1 filter
  • GFAP (39) Apply GFAP filter
  • COL1A1 (38) Apply COL1A1 filter
  • Crh (37) Apply Crh filter
  • Chat (37) Apply Chat filter
  • V-nCoV2019-S (37) Apply V-nCoV2019-S filter
  • Pomc (34) Apply Pomc filter
  • PDGFRA (33) Apply PDGFRA filter
  • Il-6 (33) Apply Il-6 filter
  • Cre (33) Apply Cre filter
  • AGRP (32) Apply AGRP filter
  • PECAM1 (32) Apply PECAM1 filter
  • Npy (32) Apply Npy filter
  • Wnt5a (31) Apply Wnt5a filter
  • CXCL10 (31) Apply CXCL10 filter
  • GLP1R (31) Apply GLP1R filter
  • Sox9 (29) Apply Sox9 filter
  • CD68 (28) Apply CD68 filter
  • Penk (28) Apply Penk filter
  • PD-L1 (28) Apply PD-L1 filter
  • ACTA2 (27) Apply ACTA2 filter
  • SHH (27) Apply SHH filter
  • VGluT1 (27) Apply VGluT1 filter
  • OLFM4 (26) Apply OLFM4 filter
  • GFP (26) Apply GFP filter
  • Rbfox3 (25) Apply Rbfox3 filter
  • MALAT1 (24) Apply MALAT1 filter
  • SOX2 (24) Apply SOX2 filter
  • Ccl2 (24) Apply Ccl2 filter

Product

  • RNAscope (5) Apply RNAscope filter
  • RNAscope 2.5 HD Red assay (5) Apply RNAscope 2.5 HD Red assay filter
  • RNAscope Multiplex Fluorescent Assay (4) Apply RNAscope Multiplex Fluorescent Assay filter
  • RNAscope 2.5 LS Assay (2) Apply RNAscope 2.5 LS Assay filter
  • RNAscope 2.5 VS Assay (2) Apply RNAscope 2.5 VS Assay filter
  • BASEscope Assay RED (1) Apply BASEscope Assay RED filter
  • RNAscope 2.0 Assay (1) Apply RNAscope 2.0 Assay filter
  • RNAscope 2.5 HD Brown Assay (1) Apply RNAscope 2.5 HD Brown Assay filter
  • RNAscope 2.5 HD Duplex (1) Apply RNAscope 2.5 HD Duplex filter
  • RNAscope 2.5 HD Reagent Kit - BROWN (1) Apply RNAscope 2.5 HD Reagent Kit - BROWN filter
  • RNAscope Fluorescent Multiplex Assay (1) Apply RNAscope Fluorescent Multiplex Assay filter
  • RNAscope Multiplex fluorescent reagent kit v2 (1) Apply RNAscope Multiplex fluorescent reagent kit v2 filter

Research area

  • Neuroscience (7) Apply Neuroscience filter
  • Cancer (6) Apply Cancer filter
  • Other (4) Apply Other filter
  • Inflammation (3) Apply Inflammation filter
  • Development (2) Apply Development filter
  • Alzheimer's Disease (1) Apply Alzheimer's Disease filter
  • Bone (1) Apply Bone filter
  • Cerebral cavernous malformation (1) Apply Cerebral cavernous malformation filter
  • CGT (1) Apply CGT filter
  • Developmental (1) Apply Developmental filter
  • Eye (1) Apply Eye filter
  • Heart (1) Apply Heart filter
  • Injury (1) Apply Injury filter
  • Macular Degeneration (1) Apply Macular Degeneration filter
  • Other: Blood Vessels (1) Apply Other: Blood Vessels filter
  • Other: Eyes (1) Apply Other: Eyes filter
  • Other: Vision Loss (1) Apply Other: Vision Loss filter
  • Regeneration (1) Apply Regeneration filter
  • Retina (1) Apply Retina filter
  • Stem cell (1) Apply Stem cell filter
  • Stem Cells (1) Apply Stem Cells filter

Category

  • Publications (26) Apply Publications filter
Microglia-Specific Promoter Activities of HEXB Gene

Frontiers in cellular neuroscience

2022 Mar 10

Shah, S;Wong, LM;Ellis, K;Bodnar, B;Saribas, S;Ting, J;Wei, Z;Tang, Y;Wang, X;Wang, H;Ling, B;Margolis, DM;Garcia, JV;Hu, W;Jiang, G;
PMID: 35360489 | DOI: 10.3389/fncel.2022.808598

Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5' untranslated region (-97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at -135, -134, and -170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS.
Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Controls Endochondral Ossification through Hyaluronan Metabolism.

Am J Pathol.

2017 Mar 08

Shimoda M, Yoshida H, Mizuno S, Hirozane T, Horiuchi K, Yoshino Y, Hara H, Kanai Y, Inoue S, Ishijima M, Okada Y.
PMID: 28284715 | DOI: 10.1016/j.ajpath.2017.01.005

Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (HYBID/KIAA1199; encoded by CEMIP) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. We generated Hybid-deficient mice using the Cre/locus of crossover in P1 (loxP) system and analyzed their phenotypes. Hybid-deficient mice were viable and fertile, but their adult long bones were shorter than those of wild-type animals. Hybid-deficient mice showed lengthening of hypertrophic zone in the growth plate until 4 weeks after birth. There were fewer capillaries and osteoclasts at the chondroosseous junction in the Hybid-deficient mice compared with the wild-type mice. In situ hybridization demonstrated that Hybid was expressed by hypertrophic chondrocytes at the chondroosseous junction. Cultured primary chondrocytes expressed higher levels of Hybid than did osteoblasts or osteoclasts, and the Hybid expression in the chondrocytes was up-regulated after maturation to hypertrophic chondrocytes. High-molecular-weight HA was accumulated in the lengthened hypertrophic zone in Hybid-deficient mice. In addition, high-molecular-weight HA significantly reduced cell growth and tube formation in vascular endothelial growth factor-stimulated or -nonstimulated endothelial cells. HA metabolism by HYBID is involved in endochondral ossification during postnatal development by modulation of angiogenesis and osteoclast recruitment at the chondroosseous junction.

Epithelial Membrane Protein 2 (EMP2) Promotes VEGF-Induced Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

Invest Ophthalmol Vis Sci.

2020 Feb 07

Sun M, Wadehra M, Casero D, Lin MC, Aguirre B, Parikh S, Matynia A, Gordon L, Chu A
PMID: 32031575 | DOI: 10.1167/iovs.61.2.3

PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs as a consequence of postnatal hyperoxia exposure in premature infants, resulting in vasoproliferation in the retina. The tetraspan protein epithelial membrane protein-2 (EMP2) is highly expressed in the retinal pigment epithelium (RPE) in adults, and it controls vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line. We, therefore, hypothesized that Emp2 knockout (Emp2 KO) protects against neovascularization in murine oxygen-induced retinopathy (OIR). METHODS: Eyes were obtained from wildtype (WT) and Emp2 KO mouse pups at P7, P12, P17, and P21 after normoxia or hyperoxia (P7-P12) exposure. Following hyperoxia exposure, RNA sequencing was performed using the retina/choroid layers obtained from WT and Emp2 KO at P17. Retinal sections from P7, P12, P17, and P21 were evaluated for Emp2, hypoxia-inducible factor 1? (Hif1?), and VEGF expression. Whole mount images were generated to assess vaso-obliteration at P12 and neovascularization at P17. RESULTS: Emp2 KO OIR mice demonstrated a decrease in pathologic neovascularization at P17 compared with WT OIR mice through evaluation of retinal vascular whole mount images. This protection was accompanied by a decrease in Hif1? at P12 and VEGFA expression at P17 in Emp2 KO animals compared with the WT animals in OIR conditions. Collectively, our results suggest that EMP2 enhances the effects of neovascularization through modulation of angiogenic signaling. CONCLUSIONS: The protection of Emp2 KO mice against pathologic neovascularization through attenuation of HIF and VEGF upregulation in OIR suggests that hypoxia-induced upregulation of EMP2 expression in the neuroretina modulates HIF-mediated neuroretinal VEGF expression
VEGF stimulates intramembranous bone formation during craniofacial skeletal development

Matrix Biology

2016 Feb 18

Duan X, Bradbury SR, Olsen BR, Berendsen AD.
PMID: 26899202 | DOI: 10.1016/j.matbio.2016.02.005.

Deficiency of vascular endothelial growth factor A (VEGF) has been associated with severe craniofacial anomalies in both humans and mice. Cranial neural crest cell (NCC)-derived VEGF regulates proliferation, vascularization and ossification of cartilage and membranous bone. However, the function of VEGF derived from specific subpopulations of NCCs in controlling unique aspects of craniofacial morphogenesis is not clear. In this study a conditional knockdown strategy was used to genetically delete Vegfa expression in Osterix (Osx) and collagen II (Col2)-expressing NCC descendants. No major defects in calvaria and mandibular morphogenesis were observed upon knockdown of VEGF in the Col2+ cell population. In contrast, loss of VEGF in Osx+ osteoblast progenitor cells led to reduced ossification of calvarial and mandibular bones without affecting the formation of cartilage templates in newborn mice. The early stages of ossification in the developing jaw revealed decreased initial mineralization levels and a reduced thickness of the collagen I (Col1)-positive bone template upon loss of VEGF in Osx+ precursors. Increased numbers of proliferating cells were detected within the jaw mesenchyme of mutant embryos. Explant culture assays revealed that mandibular osteogenesis occurred independently of paracrine VEGF action and vascular development. Reduced VEGF expression in mandibles coincided with increased phospho-Smad1/5 (P-Smad1/5) levels and bone morphogenetic protein 2 (Bmp2) expression in the jaw mesenchyme. We conclude that VEGF derived from Osx+ osteoblast progenitor cells is required for optimal ossification of developing mandibular bones and modulates mechanisms controlling BMP-dependent specification and expansion of the jaw mesenchyme.

Single-cell analysis reveals inflammatory interactions driving macular degeneration

Nature communications

2023 May 05

Kuchroo, M;DiStasio, M;Song, E;Calapkulu, E;Zhang, L;Ige, M;Sheth, AH;Majdoubi, A;Menon, M;Tong, A;Godavarthi, A;Xing, Y;Gigante, S;Steach, H;Huang, J;Huguet, G;Narain, J;You, K;Mourgkos, G;Dhodapkar, RM;Hirn, MJ;Rieck, B;Wolf, G;Krishnaswamy, S;Hafler, BP;
PMID: 37147305 | DOI: 10.1038/s41467-023-37025-7

Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.
VEGFA and VEGFR2 RNAscope determination in gastric cancer.

J Mol Histol.

2018 May 14

Tamma R, Annese T, Ruggieri S, Marzullo A, Nico B, Ribatti D.
PMID: 29761299 | DOI: 10.1007/s10735-018-9777-0

Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide. Several studies on angiogenic blocking agents in gastric cancer revealing promising results by the use of monoclonal antibodies against VEGFA or its receptor VEGFR2 or against VEGFA activating pathway. The validation of biomarkers useful to better organize the clinical trials involving anti-angiogenic therapies is crucial. Molecular markers such as RNA are increasingly used for cancer diagnosis, prognosis, and therapy guidance as in the case of the targeted therapies concerning the inhibition of angiogenesis. The aim of this study is to set the conditions for evaluating the expression of VEGFA and VEGFR2 in gastric cancer specimens and in healthy gastric mucosa by the use of RNAscope, a novel RNA in situ hybridization (ISH) method that allows the visualization of a specific gene expression in individual cells. We found the increased expression of VEGFA in the tubular glands and VEGFR2 in the endothelium of gastric cancer samples mainly in the T2, T3 and T4 stages of tumor progression as compared to the healthy controls. These results obtained by the application of this highly sensitive method for oligonucleotide detection the role of angiogenesis in gastric cancer progression already highlighted by conventional immunohistochemical methods, and offer significant promise as a new platform for developing and implementing RNA-based molecular diagnostics also in the conditions in which immunohistochemistry is not applicable.

VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal cell carcinoma with TFEB gene alterations

Mod Pathol.

2018 Sep 11

Caliò A, Brunelli M, Segala D, Pedron S, Doglioni C, Argani P, Martignoni G.
PMID: 30206412 | DOI: 10.1038/s41379-018-0128-1

Amplification of vascular endothelial growth factor A (VEGFA) has been recently reported in TFEB-amplified renal cell carcinomas regardless the level of TFEB amplification. We sought to determine VEGFA amplification by fluorescent in situ hybridization (FISH) and VEGFA mRNA expression by in situ hybridization (RNAscope 2.5) in a series of 10 renal cell carcinomas with TFEB gene alterations, either amplification and/or rearrangement (t(6;11) renal cell carcinoma). TFEB gene rearrangement was demonstrated in eight cases, whereas the remaining two cases showed a high level of TFEB (> 10 copies of fluorescent signals) gene amplification without evidence of rearrangement. Among the eight t(6;11) renal cell carcinomas (TFEB-rearranged cases), one case displayed a high level of TFEB gene amplification and two showed increased TFEB gene copy number (3-4 copies of fluorescent signals). Those three cases behaved aggressively. By FISH, VEGFA was amplified in all three cases with TFEB amplification and increased VEGFA gene copy number was observed in the two aggressive cases t(6;11) renal cell carcinomas with an overlapping increased number of TFEB fluorescent signals. Overall, VEGFA mRNA expression was observed in 8 of 10 cases (80%); of these 8 cases, 3 cases showed high-level TFEB amplification, one case showed TFEB rearrangement with increased TFEB gene copy number, whereas four showed TFEB gene rearrangement without increased copy number. In summary, VEGFA amplification/increased gene copy number and VEGFA mRNA expression occur in TFEB-amplified renal cell carcinoma, but also in a subset of t(6;11) renal cell carcinoma demonstrating aggressive behavior, and in unamplified conventional t(6;11) renal cell carcinoma suggesting VEGFA as potential therapeutic target in these neoplasms even in the absence of TFEB amplification. We finally propose that all the renal tumors showing morphological characteristics suggesting t(6;11) renal cell carcinoma and all unclassified renal cell carcinomas, either high grade or low grade, should immunohistochemically be evaluated for cathepsin K and/or Melan-A and if one of them is positive, tested for TFEB gene alteration and VEGFA gene amplification.

Accelerated tumor metastasis due to IFNγ receptor-mediated dissociation of perivascular cells from blood vessels.

J Pathol.

2017 Apr 18

Ni C, Ma P, Qu L, Wu F, Hao J, Wang R, Lu Y, Yang W, Erben U, Qin Z.
PMID: 28418194 | DOI: 10.1002/path.4907

Angiostasis mediated by IFNγ is a key mechanism of anti-tumor immunity; however, the effect of IFNγ on host VEGFA-expressing cells during tumor progression is still elusive. Here, we developed transgenic mice with IFNγ receptor (IFNγR) expression under control of the Vegfa promoter (V-γR). In these mice, the IFNγ responsiveness of VEGFA -expressing cells led to a dramatic growth suppression of transplanted lung carcinoma cells. Surprisingly, increased mortality and tumor metastasis were observed in the tumor-bearing V-γR mice, in comparison to the control wild type and IFNγR-deficient mice. Further study showed that perivascular cells were VEGFA-expressing cells and potential IFNγ targets. In vivo, tumor vascular perfusion and pericyte association with blood vessels were massively disrupted in V-γR mice. In vitro, IFNγ inhibited TGF-β-signaling through upregulating SMAD7 and therefore, down-regulated N-cadherin expression in pericytes. Importantly, IFNγ neutralization in vivo using a monoclonal antibody reduced tumor metastasis. Together, the results suggest that IFNγR-mediated dissociation of perivascular cells from blood vessels contributes to the acceleration of tumor metastasis. Thus the inhibition of tumor growth via IFNγ-induced angiostasis might also accelerate tumor metastasis.

Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice

PLoS One

2019 Mar 14

Girolamo F, Errede M, Longo G, Annese T, Alias C, Ferrara G, Morando S, Trojano M, Kerlero de Rosbo N, Uccelli A and Virgintino D
PMID: 30870435 | DOI: 10.1371/journal.pone.0213508

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within the neurovascular unit (NVU), de facto intervening in its cellular and molecular composition, we quantified by immunoconfocal morphometry the presence of OPCs in contact with brain microvessels, during postnatal cerebral cortex vascularization at postnatal day 6, in wild-type (WT) and NG2 knock-out (NG2KO) mice, and in the cortex of adult naive and EAE-affected WT and NG2KO mice. As observed in WT mice during postnatal development, a higher number of juxtavascular and perivascular OPCs was revealed in adult WT mice during EAE compared to adult naive WT mice. In EAE-affected mice, OPCs were mostly associated with microvessels that showed altered claudin-5 and occludin tight junction (TJ) staining patterns and barrier leakage. In contrast, EAE-affected NG2KO mice, which did not show any significant increase in vessel-associated OPCs, seemed to retain better preserved TJs and BBB integrity. As expected, absence of NG2, in both OPCs and pericytes, led to a reduced content of vessel basal lamina molecules, laminin, collagen VI, and collagen IV. In addition, analysis of the major ligand/receptor systems known to promote OPC proliferation and migration indicated that vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor-AA (PDGF-AA), and the transforming growth factor-beta (TGF-beta) were the molecules most likely involved in proliferation and recruitment of vascular OPCs during EAE. These results were confirmed by real time-PCR that showed Fgf2, Pdgfa and Tgfb expression on isolated cerebral cortex microvessels and by dual RNAscope-immunohistochemistry/in situ hybridization (IHC/ISH), which detected Vegfa and Vegfr2 transcripts on cerebral cortex sections. Overall, this study suggests that vascular OPCs, in virtue of their developmental arrangement and response to neuroinflammation and growth factors, could be integrated among the classical NVU cell components. Moreover, the synchronized activation of vascular OPCs and pericytes during both BBB development and dysfunction, points to NG2 as a key regulator of vascular interactions.
Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing.

Scientific Reports

2018 Nov 30

Sun N, Ning B, Hansson KM, Bruce AC, Seaman SA, Zhang C, Rikard M, DeRosa CA, Fraser CL, Wågberg M, Fritsche-Danielson R, Wikström J, Chien KR, Lundahl A, Hölttä M, Carlsson LG, Peirce SM, Hu S.
PMID: - | DOI: 10.1038/s41598-018-35570-6

Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.

TP53 positivity combined with high fibrinogen expression defines a subtype of oral squamous cell carcinoma with an unfavorable prognosis

Human Pathology

2022 Oct 01

Inoue, A;Matsumoto, T;Ito, Y;Saegusa, M;Takahashi, H;
| DOI: 10.1016/j.humpath.2022.10.008

The number of deaths due to oral squamous carcinoma (OSCC), a malignant tumor of the oral cavity, is on the increase. We examined fibrinogen (FIB) expression in patients with OSCC and developed novel immunoprofile classification methods that include FIB. The plasma FIB level in patients with OSCC was elevated compared with that in patients with non-tumor oral disease (non-T); using a cut-off point of 342 mg/dL, we found the area under the curve-receiver operating characteristic level for OSCC was 0.745. Similarly, FIB expression in OSCC tissues was significantly higher compared with that in non-T tissues. Hierarchical clustering based on the immunoprofile of several markers including FIB, p53, and p16 revealed four groups that could be used to categorize OSCC cases (referred to as immunoprofile subtypes, [IPS], I-IV). Tumors in IPS-II, which were FIB+/p53+, were associated with a significantly worse overall survival (OS) when compared with the other subtypes. We conclude that our IPS classification system can facilitate prognostic evaluation in OSCC, and that quantification of FIB is an important component of the classification strategy for this disease.
Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown.

JCI Insight

2017 Feb 09

Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A.
PMID: 28194443 | DOI: 10.1172/jci.insight.90905

In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders.

Pages

  • 1
  • 2
  • 3
  • next ›
  • last »
X
Description
sense
Example: Hs-LAG3-sense
Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron#
Example: Mm-Htt-intron2
Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan
Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)
A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp
Example: Hs-PDGFB-No-XMm
Does not cross detect with the species (Sp)
XSp
Example: Rn-Pde9a-XMm
designed to cross detect with the species (Sp)
O#
Example: Mm-Islr-O1
Alternative design targeting different regions of the same transcript or isoforms
CDS
Example: Hs-SLC31A-CDS
Probe targets the protein-coding sequence only
EnEmProbe targets exons n and m
En-EmProbe targets region from exon n to exon m
Retired Nomenclature
tvn
Example: Hs-LEPR-tv1
Designed to target transcript variant n
ORF
Example: Hs-ACVRL1-ORF
Probe targets open reading frame
UTR
Example: Hs-HTT-UTR-C3
Probe targets the untranslated region (non-protein-coding region) only
5UTR
Example: Hs-GNRHR-5UTR
Probe targets the 5' untranslated region only
3UTR
Example: Rn-Npy1r-3UTR
Probe targets the 3' untranslated region only
Pan
Example: Pool
A mixture of multiple probe sets targeting multiple genes or transcripts

Enabling research, drug development (CDx) and diagnostics

Contact Us
  • Toll-free in the US and Canada
  • +1877 576-3636
  • 
  • 
  • 
Company
  • Overview
  • Leadership
  • Careers
  • Distributors
  • Quality
  • News & Events
  • Webinars
  • Patents
Products
  • RNAscope or BaseScope
  • Target Probes
  • Controls
  • Manual assays
  • Automated Assays
  • Accessories
  • Software
  • How to Order
Research
  • Popular Applications
  • Cancer
  • Viral
  • Pathways
  • Neuroscience
  • Other Applications
  • RNA & Protein
  • Customer Innovations
  • Animal Models
Technology
  • Overview
  • RNA Detection
  • Spotlight Interviews
  • Publications & Guides
Assay Services
  • Our Services
  • Biomarker Assay Development
  • Cell & Gene Therapy Services
  • Clinical Assay Development
  • Tissue Bank & Sample Procurement
  • Image Analysis
  • Your Benefits
  • How to Order
Diagnostics
  • Diagnostics
  • Companion Diagnostics
Support
  • Getting started
  • Contact Support
  • Troubleshooting Guide
  • FAQs
  • Manuals, SDS & Inserts
  • Downloads
  • Webinars
  • Training Videos

Visit Bio-Techne and its other brands

  • bio-technie
  • protein
  • bio-spacific
  • rd
  • novus
  • tocris
© 2025 Advanced Cell Diagnostics, Inc.
  • Terms and Conditions of Sale
  • Privacy Policy
  • Security
  • Email Preferences
  • 
  • 
  • 

For Research Use Only. Not for diagnostic use. Refer to appropriate regulations. RNAscope is a registered trademark; and HybEZ, EZ-Batch and DNAscope are trademarks of Advanced Cell Diagnostics, Inc. in the United States and other countries. All rights reserved. ©2025 Advanced Cell Diagnostics, Inc.

 

Contact Us / Request a Quote
Download Manuals
Request a PAS Project Consultation
Order online at
bio-techne.com
OK
X
Contact Us

Complete one of the three forms below and we will get back to you.

For Quote Requests, please provide more details in the Contact Sales form below

  • Contact Sales
  • Contact Support
  • Contact Services
  • Offices

Advanced Cell Diagnostics

Our new headquarters office starting May 2016:

7707 Gateway Blvd.  
Newark, CA 94560
Toll Free: 1 (877) 576-3636
Phone: (510) 576-8800
Fax: (510) 576-8798

 

Bio-Techne

19 Barton Lane  
Abingdon Science Park
Abingdon
OX14 3NB
United Kingdom
Phone 2: +44 1235 529449
Fax: +44 1235 533420

 

Advanced Cell Diagnostics China

20F, Tower 3,
Raffles City Changning Office,
1193 Changning Road, Shanghai 200051

021-52293200
info.cn@bio-techne.com
Web: www.acdbio.com/cn

For general information: Info.ACD@bio-techne.com
For place an order: order.ACD@bio-techne.com
For product support: support.ACD@bio-techne.com
For career opportunities: hr.ACD@bio-techne.com

See Distributors
×

You have already Quick ordered an Item in your cart . If you want to add a new item , Quick ordered Item will be removed form your cart. Do You want to continue?

OK Cancel
Need help?

How can we help you?