- Probes for (1559217)
- Kits & Accessories (135)
- Support & Documents (0)
- Publications (7110)
- Image gallery (0)
Refine Probe List
Biological Psychiatry
2022 May 01
Dzirasa, K;Ransey, E;Chesnov, K;Wisdom, E;Bowman, R;Rodriguez, T;Adamson, E;Thomas, G;Almoril-Porras, A;Schwennesen, H;Colón-Ramos, D;Hultman, R;Bursac, N;
| DOI: 10.1016/j.biopsych.2022.02.055
Background The coordination of activity between brain cells is a key determinant of neural circuit function; nevertheless, approaches that selectively regulate communication between two distinct cellular components of a circuit, while leaving the activity of the presynaptic brain cell undisturbed remain sparse. Methods To address this gap, we developed a novel class of electrical synapses by selectively engineering two connexin proteins found in Morone americana (white perch fish): connexin34.7 (Cx34.7) and connexin35 (Cx35). Results By iteratively exploiting protein mutagenesis, a novel in vitro assay of connexin docking, and computational modeling of connexin hemichannel interactions, we uncovered the pattern of structural motifs that broadly determine connexin hemichannel docking. We then utilized this knowledge to design Cx34.7 and Cx35 hemichannels that dock with each other, but not with themselves nor other major connexins expressed in the human central nervous system. We validated these hemichannels in vivo, demonstrating that they facilitate communication between two neurons in Caenorhabditis elegans and recode a learned behavioral preference. Conclusions This system can be applied to edit circuits composed by pairs of genetically defined brain cell types across multiple species. Thus, we establish a potentially translational approach, ‘Long-term integration of Circuits using connexins’ (LinCx), for context-precise circuit-editing with unprecedented spatiotemporal specificity.
Clinical cancer research : an official journal of the American Association for Cancer Research
2022 May 05
Kumar, A;Mohamed, E;Tong, S;Chen, K;Mukherjee, J;Lim, Y;Wong, CM;Boosalis, Z;Shai, A;Pieper, RO;Gupta, N;Perry, A;Bollen, AW;Molinaro, AM;Solomon, DA;Shieh, JTC;Phillips, JJ;
PMID: 35511927 | DOI: 10.1158/1078-0432.CCR-21-2830
The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T cell effector function in glioma.We used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response. We then used patient-derived glioma cultures and an immunocompetent murine model for malignant glioma to analyze the ability of tumor-intrinsic factors to promote a CD8+ T cell response.As compared with IDH-mutant astrocytoma, MAPK-activated pleomorphic xanthoastrocytoma (PXA) harbored increased numbers of activated cytotoxic CD8+ T cells and Iba1+ microglia/macrophages, increased MHC class I expression, enrichment of genes associated with antigen presentation and processing, and increased tumor cell secretion of the chemokine CXCL14. CXCL14 promoted activated CD8+ T cell chemotaxis in vitro, recruited tumor-infiltrating CD8+ T cells in vivo, and prolonged overall survival in a cytotoxic T cell-dependent manner. The immunomodulatory molecule B7-H3 was also highly expressed in PXA.We identify the MAPK-activated lower grade astrocytoma PXA, as having an immune-rich tumor microenvironment and suggest this tumor may be particularly vulnerable to immunotherapeutic modulation. We also identify CXCL14 as an important determinant of the glioma-associated immune microenvironment, sufficient to promote an anti-tumor CD8+ T cell response.
Neuro-oncology
2022 May 26
Verploegh, ISC;Conidi, A;Brouwer, RWW;Balcioglu, HE;Karras, P;Makhzami, S;Korporaal, A;Marine, JC;Lamfers, M;van IJcken, WFJ;Leenstra, S;Huylebroeck, D;
PMID: 35639831 | DOI: 10.1093/neuonc/noac143
Glioblastoma (GBM) is the most aggressive primary brain tumor. Its cellular composition is very heterogeneous, with cells exhibiting stem-cell characteristics (GSCs) that co-determine therapy resistance and tumor recurrence. Bone Morphogenetic Protein (BMP)-4 promotes astroglial and suppresses oligodendrocyte differentiation in GSCs, processes associated with superior patient prognosis. We characterized variability in cell viability of patient-derived GBM cultures in response to BMP4 and, based on single-cell transcriptome profiling, propose predictive positive and early-response markers for sensitivity to BMP4.Cell viability was assessed in 17 BMP4-treated patient-derived GBM cultures. In two cultures, one highly sensitive to BMP4 (high therapeutic efficacy) and one with low sensitivity, response to treatment with BMP4 was characterized. We applied single-cell RNA-sequencing, analyzed the relative abundance of cell clusters, searched for and identified the aforementioned two marker types, and validated these results in all 17 cultures.High variation in cell viability was observed after treatment with BMP4. In three cultures with highest sensitivity for BMP4, a substantial new cell subpopulation formed. These cells displayed decreased cell proliferation and increased apoptosis. Neuronal differentiation was reduced most in cultures with little sensitivity for BMP4. OLIG1/2 levels were found predictive for high sensitivity to BMP4. Activation of ribosomal translation (RPL27A, RPS27) was upregulated within one day in cultures that were very sensitive to BMP4.The changes in composition of patient-derived GBM cultures obtained after treatment with BMP4 correlate with treatment efficacy. OLIG1/2 expression can predict this efficacy, and upregulation of RPL27A and RPS27 are useful early-response markers.
Developmental cell
2022 May 02
van Bruggen, D;Pohl, F;Langseth, CM;Kukanja, P;Lee, H;Albiach, AM;Kabbe, M;Meijer, M;Linnarsson, S;Hilscher, MM;Nilsson, M;Sundström, E;Castelo-Branco, G;
PMID: 35523173 | DOI: 10.1016/j.devcel.2022.04.016
Oligodendrogenesis in the human central nervous system has been observed mainly at the second trimester of gestation, a much later developmental stage compared to oligodendrogenesis in mice. Here, we characterize the transcriptomic neural diversity in the human forebrain at post-conception weeks (PCW) 8-10. Using single-cell RNA sequencing, we find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level through the use of single-cell ATAC-seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of 50 key genes through the use of in situ sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mice and humans and describe regulatory mechanisms involved in human OPC specification.
Matrix biology : journal of the International Society for Matrix Biology
2022 May 07
Rekad, Z;Izzi, V;Lamba, R;Ciais, D;Van Obberghen-Schilling, E;
PMID: 35537652 | DOI: 10.1016/j.matbio.2022.05.003
The extracellular matrix (ECM) is a fundamental component of the tissue of multicellular organisms that is comprised of an intricate network of multidomain proteins and associated factors, collectively known as the matrisome. The ECM creates a biophysical environment that regulates essential cellular processes such as adhesion, proliferation and migration and impacts cell fate decisions. The composition of the ECM varies across organs, developmental stages and diseases. Interestingly, most ECM genes generate transcripts that undergo extensive alternative splicing events, producing multiple protein variants from one gene thus enhancing ECM complexity and impacting matrix architecture. Extensive studies over the past several decades have linked ECM remodeling and expression of alternatively spliced ECM isoforms to cancer, and reprogramming of the alternative splicing patterns in cells has recently been proposed as a new hallmark of tumor progression. Indeed, tumor-associated alternative splicing occurs in both malignant and non-malignant cells of the tumor environment and growing evidence suggests that expression of specific ECM splicing variants could be a key step for stromal activation. In this review, we present a general overview of alternative splicing mechanisms, featuring examples of ECM components. The importance of ECM variant expression during essential physiological processes, such as tissue organization and embryonic development is discussed as well as the dysregulation of alternative splicing in cancer. The overall aim of this review is to address the complexity of the ECM by highlighting the importance of the yet-to-be-fully-characterized "alternative" matrisome in physiological and pathological states such as cancer.
Theranostics
2022 Apr 24
Zhang, H;Su, X;Burley, SK;Zheng, XFS;
PMID: 35547764 | DOI: 10.7150/thno.72581
Background: Hepatocellular Carcinoma (HCC) is a major form of liver cancer and a leading cause of cancer-related death worldwide. New insights into HCC pathobiology and mechanism of drug actions are urgently needed to improve patient outcomes. HCC undergoes metabolic reprogramming of glucose metabolism from respiration to aerobic glycolysis, a phenomenon known as the 'Warburg Effect' that supports rapid cancer cell growth, survival, and invasion. mTOR is known to promote Warburg Effect, but the underlying mechanism(s) remains poorly defined. The aim of this study is to understand the mechanism(s) and significance of mTOR regulation of aerobic glycolysis in HCC. Methods: We profiled mTORC1-dependent long non-coding RNAs (lncRNAs) by RNA-seq of HCC cells treated with rapamycin. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the transcriptional regulation of NEAT1 by mTORC1. [U-13C]-glucose labeling and metabolomic analysis, extracellular acidification Rate (ECAR) by Seahorse XF Analyzer, and glucose uptake assay were used to investigate the role of mTOR-NEAT1-NONO signaling in the regulation of aerobic glycolysis. RNA immunoprecipitation (RIP) and NONO-binding motif scanning were performed to identify the regulatory mechanism of pre-mRNA splicing by mTOR-NEAT1. Myristoylated AKT1 (mAKT1)/NRASV12-driven HCC model developed by hydrodynamic transfection (HDT) was employed to explore the significance of mTOR-NEAT1 signaling in HCC tumorigenesis and mTOR-targeted therapy. Results: mTOR regulates lncRNA transcriptome in HCC and that NEAT1 is a major mTOR transcriptional target. Interestingly, although both NEAT1_1 and NEAT1_2 are down-regulated in HCC, only NEAT1_2 is significantly correlated with poor overall survival of HCC patients. NEAT1_2 is the organizer of nuclear paraspeckles that sequester the RNA-binding proteins NONO and SFPQ. We show that upon oncogenic activation, mTORC1 suppresses NEAT1_2 expression and paraspeckle biogenesis, liberating NONO/SFPQ, which in turn, binds to U5 within the spliceosome, stimulating mRNA splicing and expression of key glycolytic enzymes. This series of actions lead to enhanced glucose transport, aerobic glycolytic flux, lactate production, and HCC growth both in vitro and in vivo. Furthermore, the paraspeckle-mediated mechanism is important for the anticancer action of US FDA-approved drugs rapamycin/temsirolimus. Conclusions: These findings reveal a molecular mechanism by which mTOR promotes the 'Warburg Effect', which is important for the metabolism and development of HCC, and anticancer response of mTOR-targeted therapy.
Molecular therapy : the journal of the American Society of Gene Therapy
2022 May 16
Gorsuch, CL;Nemec, P;Yu, M;Xu, S;Han, D;Smith, J;Lape, J;van Buuren, N;Ramirez, R;Muench, RC;Holdorf, MM;Feierbach, B;Falls, G;Holt, J;Shoop, W;Sevigny, E;Karriker, F;Brown, RV;Joshi, A;Goodwin, T;Tam, YK;Lin, PJC;Semple, SC;Leatherbury, N;Delaney Iv, WE;Jantz, D;Rhoden Smith, A;
PMID: 35581938 | DOI: 10.1016/j.ymthe.2022.05.013
Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome. Transient ARCUS-POL expression in HBV-infected primary human hepatocytes produced substantial reductions in both cccDNA and hepatitis B surface antigen (HBsAg). To evaluate ARCUS-POL in vivo, we developed episomal adeno-associated virus (AAV) mouse and non-human primate (NHP) models containing a portion of the HBV genome serving as a surrogate for cccDNA. Clinically relevant delivery was achieved through systemic administration of lipid nanoparticles containing ARCUS-POL mRNA. In both mouse and NHP, we observed a significant decrease in total AAV copy number and high on-target indel frequency. In the case of the mouse model, which supports HBsAg expression, circulating surface antigen was durably reduced by 96%. Together, these data support a gene-editing approach for elimination of cccDNA toward an HBV cure.
Molecular therapy : the journal of the American Society of Gene Therapy
2022 May 05
Tadokoro, T;Bravo-Hernandez, M;Agashkov, K;Kobayashi, Y;Platoshyn, O;Navarro, M;Marsala, S;Miyanohara, A;Yoshizumi, T;Shigyo, M;Krotov, V;Juhas, S;Juhasova, J;Nguyen, D;Kupcova Skalnikova, H;Motlik, J;Studenovska, H;Proks, V;Reddy, R;Driscoll, SP;Glenn, TD;Kemthong, T;Malaivijitnond, S;Tomori, Z;Vanicky, I;Kakinohana, M;Pfaff, SL;Ciacci, J;Belan, P;Marsala, M;
PMID: 35524407 | DOI: 10.1016/j.ymthe.2022.04.023
Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.
Proceedings of the National Academy of Sciences of the United States of America
2022 May 24
Eltobgy, MM;Zani, A;Kenney, AD;Estfanous, S;Kim, E;Badr, A;Carafice, C;Daily, K;Whitham, O;Pietrzak, M;Webb, A;Kawahara, J;Eddy, AC;Denz, P;Lu, M;Kc, M;Peeples, ME;Li, J;Zhu, J;Que, J;Robinson, R;Rosas Mejia, O;Rayner, RE;Hall-Stoodley, L;Seveau, S;Gavrilin, MA;Zhang, X;Thomas, J;Kohlmeier, JE;Suthar, MS;Oltz, E;Tedeschi, A;Robledo-Avila, FH;Partida-Sanchez, S;Hemann, EA;Abdelrazik, E;Forero, A;Nimjee, SM;Boyaka, PN;Cormet-Boyaka, E;Yount, JS;Amer, AO;
PMID: 35588457 | DOI: 10.1073/pnas.2202012119
SignificanceWe report the discovery of fundamental roles for the noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role in immune responses beyond its previously appreciated effects in bacterial infections. Further, we show that Caspase-11-deficient mice infected with SARS-CoV-2 fare significantly better in terms of overall illness, lung inflammation, and thrombosis than wild-type (WT) mice, thus implicating Caspase-11 as a new therapeutic target for preventing or treating COVID-19.
Proceedings of the National Academy of Sciences of the United States of America
2022 May 24
Veleanu, M;Urrieta-Chávez, B;Sigoillot, SM;Paul, MA;Usardi, A;Iyer, K;Delagrange, M;Doyle, JP;Heintz, N;Bécamel, C;Selimi, F;
PMID: 35588456 | DOI: 10.1073/pnas.2122544119
SignificanceSynaptogenesis and neural network remodeling are at their maximum during the perinatal period of human brain development. Perturbations of this highly sensitive stage might underlie the etiology of neurodevelopmental disorders. Subchronic neonatal administration of phencyclidine, a drug of abuse, has been used to model schizophrenia in rodents. In this model, we found specific long-term synaptic changes in Purkinje cells and transient gene expression changes in the cerebellum. While transient increased neuronal activity in the cerebellum, induced using chemogenetics, reproduces some phencyclidine-induced molecular changes, it is insufficient to reproduce the long-term synaptic effects. Our results show the complex mechanism of action of phencyclidine on the development of neuronal connectivity and further highlight the potential contribution of cerebellar defects in psychiatric diseases.
Current biology : CB
2022 May 02
Gerstmann, K;Jurčić, N;Blasco, E;Kunz, S;de Almeida Sassi, F;Wanaverbecq, N;Zampieri, N;
PMID: 35512696 | DOI: 10.1016/j.cub.2022.04.019
From swimming to walking and flying, animals have evolved specific locomotor strategies to thrive in different habitats. All types of locomotion depend on the integration of motor commands and sensory information to generate precisely coordinated movements. Cerebrospinal-fluid-contacting neurons (CSF-cN) constitute a vertebrate sensory system that monitors CSF composition and flow. In fish, CSF-cN modulate swimming activity in response to changes in pH and bending of the spinal cord; however, their role in mammals remains unknown. We used mouse genetics to study their function in quadrupedal locomotion. We found that CSF-cN are directly integrated into spinal motor circuits. The perturbation of CSF-cN function does not affect general motor activity nor the generation of locomotor rhythm and pattern but results in specific defects in skilled movements. These results identify a role for mouse CSF-cN in adaptive motor control and indicate that this sensory system evolved a novel function to accommodate the biomechanical requirements of limb-based locomotion.
Kidney international
2022 May 26
Kaneko, K;Sato, Y;Uchino, E;Toriu, N;Shigeta, M;Kiyonari, H;Endo, S;Fukuma, S;Yanagita, M;
PMID: 35644281 | DOI: 10.1016/j.kint.2022.04.026
Erythropoietin (Epo) is produced by a subpopulation of resident fibroblasts in the healthy kidney. We have previously demonstrated that, during kidney fibrosis, kidney fibroblasts including Epo-producing cells transdifferentiate into myofibroblasts and lose their Epo-producing ability. However, it remains unclear whether Epo-producing cells survive and transform into myofibroblasts during fibrosis because previous studies did not specifically label Epo-producing cells in pathophysiological conditions. Here, we generated EpoCreERT2/+ mice, a novel mouse strain that enables labeling of Epo-producing cells at desired time points and examined the behaviors of Epo-producing cells under pathophysiological conditions. Lineage -labeled cells that were producing Epo when labeled were found to be a small subpopulation of fibroblasts located in the interstitium of the kidney, and their number increased during phlebotomy-induced anemia. Around half of lineage-labeled cells expressed Epo mRNA, and this percentage was maintained even 16 weeks after recombination, supporting the idea that a distinct subpopulation of cells with Epo-producing ability makes Epo repeatedly. During fibrosis caused by ureteral obstruction, EpoCreERT2/+ -labeled cells were found to transdifferentiate into myofibroblasts with concomitant loss of Epo-producing ability, and their numbers and the proportion among resident fibroblasts increased during fibrosis, indicating their high proliferative capacity. Finally, we confirmed that EpoCreERT2/+-labeled cells that lost their Epo-producing ability during fibrosis regained their ability after kidney repair due to relief of the ureteral obstruction. Thus, our analyses have revealed previously unappreciated characteristic behaviors of Epo-producing cells, which had not been clearly distinguished from those of resident fibroblasts.
Pages
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 | |
| EnEm | Probe targets exons n and m | |
| En-Em | Probe 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 | |
- Toll-free in the US and Canada
- +1877 576-3636
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
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
×
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