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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.

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Unveiling Complexity and Multipotentiality of Early Heart Fields

Circulation research

2021 Jun 24

Zhang, Q;Carlin, D;Zhu, F;Cattaneo, P;Ideker, T;Evans, SM;Bloomekatz, J;Chi, NC;
PMID: 34162224 | DOI: 10.1161/CIRCRESAHA.121.318943

Rationale: Extraembryonic tissues, including the yolk sac and placenta, and the heart within the embryo, work to provide crucial nutrients to the embryo. The association of congenital heart defects (CHDs) with extraembryonic tissue defects further supports the potential developmental relationship between the heart and extraembryonic tissues. Although the development of early cardiac lineages has been well-studied, the developmental relationship between cardiac lineages, including epicardium, and extraembryonic mesoderm remains to be defined. Objective: To explore the developmental relationships between cardiac and extraembryonic lineages. Methods and Results: Through high-resolution single cell and genetic lineage/clonal analyses, we show an unsuspected clonal relationship between extraembryonic mesoderm and cardiac lineages. Single-cell transcriptomics and trajectory analyses uncovered two mesodermal progenitor sources contributing to left ventricle cardiomyocytes, one embryonic and the other with an extraembryonic gene expression signature. Additional lineage-tracing studies revealed that the extraembryonic-related progenitors reside at the embryonic-extraembryonic interface in gastrulating embryos, and produce distinct cell types forming the pericardium, septum transversum, epicardium, dorsolateral regions of the left ventricle and atrioventricular canal myocardium, and extraembryonic mesoderm. Clonal analyses demonstrated that these progenitors are multipotent, giving rise to not only cardiomyocytes and serosal mesothelial cell types but also, remarkably, extraembryonic mesoderm. Conclusions: Overall, our results reveal the location of previously unknown multipotent cardiovascular progenitors at the embryonic-extraembryonic interface, and define the earliest embryonic origins of serosal mesothelial lineages, including the epicardium, which contributes fibroblasts and vascular support cells to the heart. The shared lineage relationship between embryonic cardiovascular lineages and extraembryonic mesoderm revealed by our studies underscores an underappreciated blurring of boundaries between embryonic and extraembryonic mesoderm. Our findings suggest unexpected underpinnings of the association between congenital heart disease and placental insufficiency anomalies, and the potential utility of extraembryonic cells for generating cardiovascular cell types for heart repair.
Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma

Head and neck pathology

2021 May 26

Saab-Chalhoub, MW;Guo, X;Shi, Q;Chernock, RD;Lewis, JS;
PMID: 34041710 | DOI: 10.1007/s12105-021-01335-3

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.
Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer

Cancer

2021 Jan 11

Drake, VE;Fakhry, C;Windon, MJ;Stewart, CM;Akst, L;Hillel, A;Chien, W;Ha, P;Miles, B;Gourin, CG;Mandal, R;Mydlarz, WK;Rooper, L;Troy, T;Yavvari, S;Waterboer, T;Brenner, N;Eisele, DW;D'Souza, G;
PMID: 33426652 | DOI: 10.1002/cncr.33346

Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex intensity (>5 sex-years: aOR, 2.8 [95% CI, 1.1-7.5]) remained associated with significantly increased odds of HPV-OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1-2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1-2.4]) was associated with HPV-OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122-670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70-378]) was associated with increased odds of HPV-OPC. Number of oral sex partners remains a strong risk factor for HPV-OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV-OPC.
Patch‐to‐Seq Reveals Unique Transcriptomic Profiles of Chemosensitive Serotonergic Neurons

The FASEB Journal

2021 Jan 01

Mouradian, G;Duffy, E;Liu, P;Gomez‐Vargas, J;
| DOI: 10.1096/fasebj.2021.35.S1.04448

Central respiratory chemoreceptors are specialized neurons with intrinsic sensitivity to hypercapnia and/or acidosis that couple breathing and pH/CO2 levels. Prior data indicate that a sub-population of brainstem serotonin (5-HT) neurons are likely central respiratory chemoreceptors. However, it remains unclear which 5-HT neurons develop chemosensitivity and what molecular markers may identify this unique sub-population of 5-HT neurons. Here we employed the “patch-to-seq” technique to measure action potential firing rate responses of 5-HT neuron to hypercapnic acidosis using cell-attached patch-clamp electrophysiology followed by isolation of that neurons’ intracellular RNA content for single cell RNA Sequencing. Acute brainstem slices (200 µm) from young (P18-23) transgenic rats expressing eGFP in all 5-HT neurons (SSeGFP) were recorded while superfused with artificial CSF (aCSF) containing inhibitors for synaptic blockade (10 mM CNQX, 50 mM D-AP5, 20 mM Gabazine) bubbled with either 5% CO2 (bal. O2; pH= 7.36; 5 min) or 15% CO2 (bal. O2; pH= 7.10). The Chemosensitivity Index (C.I.) determined cell phenotypes. pH-sensitive eGFP+ neurons (n=48) had an average C.I. of 169.8± 8.25 SEM whereas pH-insensitive eGFP+ neurons (n=44) had an average C.I. of 100.3 ± 1.4 (P < 0.0001; t-test). Cell extracts from 11 chemosensitive and 10 insensitive recorded cells were subjected to single cell RNA Sequencing (scRNA-Seq), from which an average of 48.3M reads were generated with a quality score of ~32.7 and ~75% mapping rate per sample with an average of ~8,000 genes detected. Purity of the isolated samples was confirmed by significantly more expression (Log2(FPKM+1)) of 6 serotonergic vs 7 neuronal and 8 glial gene markers, and more expression of 7 neuronal vs 8 known glial gene markers. There were 166differentially expressed genes (q < 0.05) between pH-sensitive and -insensitive 5-HT neuron populations none of which have a known contribution to pH regulation or sensing. Predicted upstream regulators of 352 DEGs (p
PD-L1 expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer

J Thorac Oncol.

2016 Sep 14

Yu H, Batenchuk C, Badzio A, Boyle TA, Czapiewski P, Chan DC, Lu X, Gao D, Ellison K, Kowalewski AA, Rivard CJ, Dziadziuszko R, Zhou C, Hussein M, Richards D, Wilks S, Monte M, Edenfield W, Goldschmidt J, Page R, Ulrich B, Waterhouse D, Close S, Jassem J,
PMID: 27639678 | DOI: 10.1016/j.jtho.2016.09.002

This article does not have an abstract to display.

Prognostic utility of HPV specific testing in addition to p16 immunohistochemistry in oropharyngeal squamous cell carcinoma.

Ann Oncol.

2018 Aug 08

Sathasivam HP, Santambrogio A, Andoniadou CL, Robinson M, Thavaraj S.
PMID: 30101315 | DOI: 10.1093/annonc/mdy313

IgD-transcript positive cells suggest hypersensitivity in feed-related intestinal inflammation in the Atlantic salmon

Fish & shellfish immunology

2022 Dec 14

Bjørgen, H;Oaland, Ø;Midtllyng, P;Tafalla, C;Krogdahl, Å;Koppang, EO;
PMID: 36528310 | DOI: 10.1016/j.fsi.2022.108469

Specification of neuronal subtypes in the spiral ganglion begins prior to birth in the mouse

Proceedings of the National Academy of Sciences of the United States of America

2022 Nov 29

Sanders, TR;Kelley, MW;
PMID: 36409884 | DOI: 10.1073/pnas.2203935119

The afferent innervation of the cochlea is comprised of spiral ganglion neurons (SGNs), which are characterized into four subtypes (Type 1A, B, and C and Type 2). However, little is known about the factors and/or processes that determine each subtype. Here, we present a transcriptional analysis of approximately 5,500 single murine SGNs collected across four developmental time points. All four subtypes are transcriptionally identifiable prior to the onset of coordinated spontaneous activity, indicating that the initial specification process is under genetic control. Trajectory analysis indicates that SGNs initially split into two precursor types (Type 1A/2 and Type 1B/C), followed by subsequent splits to give rise to four transcriptionally distinct subtypes. Differential gene expression, pseudotime, and regulon analyses were used to identify candidate transcription factors which may regulate the subtypes specification process. These results provide insights into SGN development and comprise a transcriptional atlas of SGN maturation across the prenatal period.
In situ detection of vaccine mRNA in the cytoplasm of hepatocytes during COVID19 vaccine-related hepatitis

Journal of hepatology

2022 Sep 15

Martin-Navarro, L;de Andrea, C;Sangro, B;Argemi, J;
PMID: 36116717 | DOI: 10.1016/j.jhep.2022.08.039

von Willebrand Factor Is Produced Exclusively by Endothelium, Not Neointima, in Occlusive Vascular Lesions in Both Pulmonary Hypertension and Atherosclerosis

Circulation

2022 Aug 02

Steffes, LC;Cheng, P;Quertermous, T;Kumar, ME;
PMID: 35914017 | DOI: 10.1161/CIRCULATIONAHA.121.058427

078 Transcript profiling for TSLP in human squamous cell carcinoma in situ

Journal of Investigative Dermatology

2022 Aug 01

Suzuki-Horiuchi, Y;Prouty, S;Wushanley, L;Lee, V;Seykora, J;
| DOI: 10.1016/j.jid.2022.05.013

Abstract Unavailable
165: MUTATIONS IN MEN1 GENE ALTER ITS PROTEIN MENIN FUNCTIONS IN HUMAN GASTRINOMA; STRUCTURE-FUNCTION STUDIES OF MENIN.

Gastroenterology

2022 May 01

Sheriff, S;Duan, S;Diaz, A;Merchant, J;
| DOI: 10.1016/S0016-5085(22)60076-3

Abstract Unavailable

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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

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