Spatial and temporal expression of PORCN is highly dynamic in the developing mouse cochlea

Gene expression patterns : GEP

2021 Sep 20

Oliver, BL;Young, CA;Munnamalai, V;
PMID: 34547456 | DOI: 10.1016/j.gep.2021.119214

The mammalian organ of Corti is a highly specialized sensory organ of the cochlea with a fine-grained pattern that is essential for auditory function. The sensory epithelium, the organ of Corti consists of a single row of inner hair cells and three rows of outer hair cells that are intercalated by support cells in a mosaic pattern. Previous studies show that the Wnt pathway regulates proliferation, promotes medial compartment formation in the cochlea, differentiation of the mechanosensory hair cells and axon guidance of Type II afferent neurons. WNT ligand expressions are highly dynamic throughout development but are insufficient to explain the roles of the Wnt pathway. We address a potential way for how WNTs specify the medial compartment by characterizing the expression of Porcupine (PORCN), an O-acyltransferase that is required for WNT secretion. We show PORCN expression across embryonic ages (E)12.5 - E14.5, E16.5, and postnatal day (P)1. Our results showed enriched PORCN in the medial domains during early stages of development, indicating that WNTs have a stronger influence on patterning of the medial compartment. PORCN was rapidly downregulated after E14.5, following the onset of sensory cell differentiation; residual expression remained in some hair cells and supporting cells. On E14.5 and E16.5, we also examined the spatial expression of Gsk3β, an inhibitor of canonical Wnt signaling to determine its potential role in radial patterning of the cochlea. Gsk3β was broadly expressed across the radial axis of the epithelium; therefore, unlikely to control WNT-mediated medial specification. In conclusion, the spatial expression of PORCN enriches WNT secretion from the medial domains of the cochlea to influence the specification of cell fates in the medial sensory domain.

Spatial Transcriptomics analysis of uterine gene expression in enhancer of Zeste homolog 2 (Ezh2) conditional knockout mice

Biology of reproduction

2021 Aug 03

Mesa, AM;Mao, J;Medrano, TI;Bivens, NJ;Jurkevich, A;Tuteja, G;Cooke, PS;Rosenfeld, CS;
PMID: 34344022 | DOI: 10.1093/biolre/ioab147

Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNAseq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and/or ablation of this gene would disrupt normal epithelial/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide the mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.

PD-L1 AND FOXP3 EXPRESSION IN ORAL DYSPLASTIC TISSUES AND ORAL SQUAMOUS CELL CARCINOMA

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

2021 Jul 01

Arora, S;Wan, Z;Dong, F;Kalmadin, N;De Silva, H;Seo, B;Hussaini, H;Rich, A;
| DOI: 10.1016/j.oooo.2021.03.043

Background Oral squamous cell carcinoma (OSCC) is an aggressive, highly immunosuppressive cancer with a high mortality rate. Interactions between programmed cell death protein 1 (PD-1; on T cells) and programmed death ligand 1 (PD-L1; on tumor cells) within the tumor microenvironment facilitates T-lymphocyte exhaustion. Regulatory T cells (Treg) are a distinct lymphocyte population, expressing the transcription factor forkhead homeobox protein-3 (FoxP3), which downregulates immune responses in OSCC. PD-L1+ tumor cells and FoxP3+ Treg expression in OSCC has been associated with poor prognosis. This research investigates the expression of PD-L1+ cells and Tregs in control, dysplastic, and OSCC tissues. Objective To investigate and compare the expression of PD-L1+ tumor cells and FoxP3+ Tregs in nondysplastic tisssue, dysplastic tissue, and OSCC using immunohistochemistry. Methods Immunohistochemistry was performed on formalin-fixed, paraffin-embedded, archival tissues. Qualitative and quantitative analyses of positively stained cells were undertaken and the dysplastic (n = 20) and OSCC groups (n = 20) were compared against the non-dysplastic control group (n = 20), using image analysis Results A higher proportion score and immunoreactive score for PD-L1+ and FoxP3+ Tregs was found in OSCC and dysplastic groups when compared to the nondysplastic control group (P < .05). There was no significant difference between the OSCC and dysplastic tissues. Conclusions Significantly more PD-L1+ cells and Tregs were detected in dysplastic and OSCC tissues. An increase in PD-L1 and FoxP3 expression may serve as an indicator of progression from normal to a potentially malignant lesion.

Morphine Induces a Neuroimmune Response in Healthy Volunteers: Implications for Opioid Use Disorder

Biological Psychiatry

2021 May 01

Woodcock, E;Angarita, G;Matuskey, D;Ropchan, J;Nabulsi, N;Huang, Y;Hillmer, A;Carson, R;Cosgrove, K;
| DOI: 10.1016/j.biopsych.2021.02.632

Background: Preclinical studies indicate opioid administration evokes pro-inflammatory responses in both the periphery and brain. Opioid-induced pro-inflammatory responses influence both appetitive and dysphoric addiction processes and thus, may influence the development of opioid use disorder (OUD) and/or perpetuate continued opioid use among OUD patients. Herein, we investigated the neuroimmune effects of morphine administration using Positron Emission Tomography (PET) imaging with [11C]PBR28, a radiotracer that binds to the 18kDa translocator protein (TSPO), a marker sensitive to immune stimuli. Methods: Healthy individuals with prior medical opioid exposure (N¼4; 3M; 2 ‘high-affinity’ binders; Age¼30yrs [range¼26-38]; BMI¼26.5 [range¼24-30]) completed two Cold Pressor tasks and [11C]PBR28 PET scans (120min acquisition) in one day: one before and one after intramuscular morphine (0.07mg/kg). Arterial blood was acquired to measure the metabolite-corrected input function. Total volume of distribution (VT), i.e., TSPO availability, was estimated in 10 brain regions using multilinear analysis-1 (MA-1; t*¼30). Morphine’s effect on regional [11C]PBR28 VT was evaluated using a repeated-measures analysis of variance with rs6971 genotype as a fixed factor. Results: Morphine increased TSPO availability by 28%-39% across regions, F(1,2)¼9.56, p¼.09, partial h2¼0.83, ‘very large’ effect. Morphine increased hand withdrawal latency on the Cold Pressor task, F(1,2)¼3.98, p¼.18, partial h2¼0.66, ‘very large’ effect. Conclusions: Preliminary findings suggest that an analgesic morphine dose (4.69-5.95mg) induced a whole-brain neuroimmune response in healthy adults, the first such evidence in people. If confirmed, our findings suggest a plausible role for the neuroimmune system in the development of OUD. Future studies are needed to investigate opioid-neuroimmune relationships in OUD patients.

Opioid Use Predicts Self-Reported Mobility in Older Adults with Chronic Lower Back Pain

The Journal of Pain

2021 May 01

Buchanan, T;Rumble, D;Watts, K;DeJesus, D;Quinn, T;Buford, T;Goodin, B;
| DOI: 10.1016/j.jpain.2021.03.053

Chronic low back pain (cLBP) prevalence increases with advancing age and is a leading contributor to mobility disability among older adults. Opioids are commonly prescribed treatments to reduce pain related symptoms. The rise in opioid use and misuse can enhance a variety of issues in the adult population; such as, lack of mobility and decrease in overall health and wellbeing. Few studies have examined the impact of opioid use on mobility in older adults with cLBP. Therefore, we sought to examine the relationship between self-reported opioid use and self-reported mobility. cLBP participants (n = 140) completed a series of questionnaires regarding pain intensity, interference, and disability including demographics, clinical pain assessment, and the Brief Pain Inventory-Short form. Pearson's chi-square tests, and regression-based analyses were conducted using SPSS version 26.0. Among cLBP participants, those who self-reported opioid use were more likely to have greater self-reported difficulty climbing stairs (χ2 = 16.6, p < .05), walking for fifteen minutes (χ2 = 17.7, p < .05), performing chores (χ2 = 15.4, p < .05), and running errands (χ2 = 10.7, p < .05). Among the older cLBP participants above the age of 54 (n = 38), half used an opioid (n = 19) at some point of time as a form of cLBP pain treatment. Among older adults, opioid use was significantly associated with poorer self-reported outcomes for climbing stairs (Wald χ2(1) = 5.9, p < .05), walking (Wald χ2(1) = 7.4, p < .05), and performing chores (Wald χ2(1) = 7.5, p < .05). Opioid use predicts poorer self-reported mobility among adults and older adults with cLBP. Results inform associations between pain treatment and mobility in aging populations. Future research should seek to understand the influence of opioids on objective performance measures in cLBP. This work was supported by Examining Racial And SocioEconomic Disparities in cLBP; ERASED; R01MD010441.

BMP pathway antagonism by Grem1 regulates epithelial cell fate in intestinal regeneration

Gastroenterology

2021 Apr 01

Koppens, M;Davis, H;Valbuena, G;Mulholland, E;Nasreddin, N;Colombe, M;Antanaviciute, A;Biswas, S;Friedrich, M;Lee, L;Wang, L;Koelzer, V;East, J;Simmons, A;Winton, D;Leedham, S;
| DOI: 10.1053/j.gastro.2021.03.052

Background and aims In homeostasis, intestinal cell fate is controlled by balanced gradients of morphogen signalling. The Bone Morphogenetic Protein (BMP) pathway has a physiological, pro-differentiation role, predominantly inferred through previous experimental pathway inactivation. Intestinal regeneration is underpinned by dedifferentiation and cell plasticity, but the signalling pathways that regulate this adaptive reprogramming are not well understood. We assessed the BMP signalling landscape, and investigated the impact and therapeutic potential, of pathway manipulation in homeostasis and regeneration. Methods A novel mouse model was generated to assess the effect of autocrine Bmp4 ligand on individual secretory cell fate. We spatiotemporally mapped BMP signalling in mouse and human regenerating intestine. Transgenic models were used to explore the functional impact of pathway manipulation on stem cell fate and intestinal regeneration. Results In homeostasis, ligand exposure reduced proliferation, expedited terminal differentiation, abrogated secretory cell survival and prevented dedifferentiation. Following ulceration, physiological attenuation of BMP signalling arose through upregulation of the secreted antagonist, Grem1, from topographically distinct populations of fibroblasts. Concomitant expression supported functional compensation following Grem1 deletion from tissue-resident cells. BMP pathway manipulation showed that antagonist-mediated BMP attenuation was obligatory, but functionally sub-maximal, as regeneration was impaired or enhanced by epithelial overexpression of Bmp4 or Grem1 respectively. Mechanistically, Bmp4 abrogated regenerative stem cell reprogramming, despite a convergent impact of YAP/TAZ on cell fate in remodelled wounds. Conclusions BMP signalling prevents epithelial de-differentiation, and pathway attenuation, through stromal Grem1 upregulation, was required for adaptive reprogramming in intestinal regeneration. This intercompartmental antagonism was functionally sub-maximal, raising the possibility of therapeutic pathway manipulation in Inflammatory Bowel Disease.

Sex differences in population dynamics during formation of kidney bacterial communities by uropathogenic Escherichia coli

Infection and immunity

2021 Jan 19

McLellan, LK;Daugherty, AL;Hunstad, DA;
PMID: 33468577 | DOI: 10.1128/IAI.00716-20

Uropathogenic Escherichia coli (UPEC), the primary etiologic agent of urinary tract infections (UTIs), encounters a restrictive population bottleneck within the female mammalian bladder. Its genetic diversity is restricted during establishment of cystitis because successful UPEC must invade superficial bladder epithelial cells prior to forming clonal intracellular bacterial communities (IBCs). Here, we aimed to understand UPEC population dynamics during ascending pyelonephritis, namely formation of kidney bacterial communities (KBCs) in the renal tubular lumen and nucleation of renal abscesses. We inoculated the bladders of both male and female C3H/HeN mice, a background which features vesicoureteral reflux; we have previously shown that in this model, males develop severe, high-titer pyelonephritis and renal abscesses much more frequently than females. Mice were infected with 40 isogenic, PCR-tagged ("barcoded") UPEC strains, and tags remaining in bladder and kidneys were ascertained at intervals following infection. In contrast to females, males maintained a majority of strains within both the bladder and kidneys throughout the course of infection, indicating only a modest host-imposed bottleneck on overall population diversity during successful renal infection. Moreover, the diverse population in the infected male kidneys obscured any restrictive bottleneck in the male bladder. Finally, using RNA-in situ hybridization following mixed infections with isogenic UPEC bearing distinct markers, we found that despite their extracellular location (in the urinary space), KBCs are clonal in origin. This finding indicates that even with bulk reflux of infected bladder urine into the renal pelvis, successful ascension of UPEC to establish the tubular niche is an uncommon event.

An Atoh1 CRE knock-in mouse labels motor neurons involved in fine motor control

eNeuro

2021 Jan 14

Ogujiofor, OW;Pop, IV;Espinosa, F;Durodoye, RO;Viacheslavov, ML;Jarvis, R;Landy, MA;Gurumurthy, CB;Lai, HC;
PMID: 33468540 | DOI: 10.1523/ENEURO.0221-20.2021

Motor neurons (MNs) innervating the digit muscles of the intrinsic hand and foot (IH and IF) control fine motor movements. The ability to reproducibly label specifically IH and IF MNs in mice would be a beneficial tool for studies focused on fine motor control. To this end, we find that a CRE knock-in mouse line of Atoh1, a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, reliably expresses CRE-dependent reporter genes in approximately 60% of the IH and IF MNs. We determine that CRE-dependent expression in IH and IF MNs is ectopic because an Atoh1 mouse line driving FLPo recombinase does not label these MNs even though other Atoh1-lineage neurons in the intermediate spinal cord are reliably identified. Furthermore, the CRE-dependent reporter expression is enriched in the IH and IF MN pools with much sparser labeling of other limb-innervating MN pools such as the tibialis anterior, gastrocnemius, quadricep, and adductor. Lastly, we find that ectopic reporter expression begins postnatally and labels a mixture of alpha and gamma-MNs. Altogether, the Atoh1 CRE knock-in mouse strain might be a useful tool to explore the function and connectivity of MNs involved in fine motor control when combined with other genetic or viral strategies that can restrict labeling specifically to the IH and IF MNs. Accordingly, we provide an example of sparse labeling of IH and IF MNs using an intersectional genetic approach.Significance Statement Motor neurons (MNs) of the intrinsic hand and foot (IH and IF) are reproducibly labeled in an ectopic manner postnatally using a CRE knock-in mouse line of the basic helix-loop-helix (bHLH) transcription factor Atoh1, serving as a useful genetic tool for future studies of fine motor control.

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

EBioMedicine

2021 Jan 01

Maccio, U;Zinkernagel, AS;Shambat, SM;Zeng, X;Cathomas, G;Ruschitzka, F;Schuepbach, RA;Moch, H;Varga, Z;
PMID: 33422990 | DOI: 10.1016/j.ebiom.2020.103182

SARS-CoV-2 infection (COVID-19 disease) can induce systemic vascular involvement contributing to morbidity and mortality. SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor. The anatomical involvement of the coronary tree is not explored yet. Cardiac autopsy tissue of the entire coronary tree (main coronary arteries, epicardial arterioles/venules, epicardial capillaries) and epicardial nerves were analyzed in COVID-19 patients (n = 6). All anatomical regions were immunohistochemically tested for ACE2, TMPRSS2, CD147, CD45, CD3, CD4, CD8, CD68 and IL-6. COVID-19 negative patients with cardiovascular disease (n = 3) and influenza A (n = 6) served as controls. COVID-19 positive patients showed strong ACE2 / TMPRSS2 expression in capillaries and less in arterioles/venules. The main coronary arteries were virtually devoid of ACE2 receptor and had only mild intimal inflammation. Epicardial capillaries had a prominent lympho-monocytic endotheliitis, which was less pronounced in arterioles/venules. The lymphocytic-monocytic infiltrate strongly expressed CD4, CD45, CD68. Peri/epicardial nerves had strong ACE2 expression and lympho-monocytic inflammation. COVID-19 negative patients showed minimal vascular ACE2 expression and lacked endotheliitis or inflammatory reaction. ACE2 / TMPRSS2 expression and lymphomonocytic inflammation in COVID-19 disease increases crescentically towards the small vessels suggesting that COVID-19-induced endotheliitis is a small vessel vasculitis not involving the main coronaries. The inflammatory neuropathy of epicardial nerves in COVID-19 disease provides further evidence of an angio- and neurotrophic affinity of SARS-COV2 and might potentially contribute to the understanding of the high prevalence of cardiac complications such as myocardial injury and arrhythmias in COVID-19. No external funding was necessary for this study.

FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats

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

2022 Oct 25

Nambulli, S;Rennick, LJ;Acciardo, AS;Tilston-Lunel, NL;Ho, G;Crossland, NA;Hardcastle, K;Nieto, B;Bainbridge, G;Williams, T;Sharp, CR;Duprex, WP;
PMID: 36251995 | DOI: 10.1073/pnas.2209405119

Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the Paramyxovirus family. We determined the complete sequence of FeMVUS5 directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses. First, the virus lacks the canonical polybasic furin cleavage signal in the fusion (F) glycoprotein. Second, conserved amino acids in the hemagglutinin (H) glycoprotein used by all other morbilliviruses for binding and/or fusion activation with the cellular receptor CD150 (signaling lymphocyte activation molecule [SLAM]/F1) are absent. We show that, despite this sequence divergence, FeMV H glycoprotein uses feline CD150 as a receptor and cannot use human CD150. We demonstrate that the protease responsible for cleaving the FeMV F glycoprotein is a cathepsin, making FeMV a unique morbillivirus and more similar to the closely related zoonotic Nipah and Hendra viruses. We developed a reverse genetics system for FeMVUS5 and generated recombinant viruses expressing Venus fluorescent protein from an additional transcription unit located either between the phospho-protein (P) and matrix (M) genes or the H and large (L) genes of the genome. We used these recombinant FeMVs to establish a natural infection and demonstrate that FeMV causes an acute morbillivirus-like disease in the cat. Virus was shed in the urine and detectable in the kidneys at later time points. This opens the door for long-term studies to address the postulated role of this morbillivirus in the development of chronic kidney disease.

Exposure to chronic stress impairs the ability to cope with an acute challenge: Modulation by lurasidone treatment

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

2022 Jul 10

Begni, V;Pisano, I;Marizzoni, M;Marchisella, F;Creutzberg, KC;De Rosa, F;Cattaneo, A;Gruca, P;Litwa, E;Papp, M;Riva, MA;
PMID: 35830759 | DOI: 10.1016/j.euroneuro.2022.06.005

Chronic stress represents a major contributor for the development of mental illness. This study aimed to investigate how animals exposed to chronic mild stress (CMS) responded to an acute stress (AS), as a vulnerability's challenge, and to establish the potential effects of the antipsychotic drug lurasidone on such mechanisms. Adult male Wistar rats were exposed or not (controls) to a CMS paradigm for 7 weeks. Starting from the end of week 2, animals were randomized to receive vehicle or lurasidone for 5 weeks. Sucrose intake was used to measure anhedonia. At the end, half of the animals were exposed to an acute stress before sacrifice. Exposure to CMS produced a significant reduction in sucrose consumption, whereas lurasidone progressively normalized such alteration. We found that exposure to AS produced an upregulation of Brain derived neurotrophic factor (Bdnf) in the prefrontal cortex of controls animals. This response was impaired in CMS rats and restored by lurasidone treatment. While in control animals, AS-induced increase of Bdnf mRNA levels was specific for Parvalbumin cells, CMS rats treated with lurasidone show a significant upregulation of Bdnf in pyramidal cells. Furthermore, when investigating the activation of different brain regions, CMS rats showed an impairment in the global response to the acute stressor, that was largely restored by lurasidone treatment. Our results suggest that lurasidone treatment in CMS rats may regulate specific circuits and mechanisms, which will ultimately contribute to boost resilience under stressful challenges.

Gradual decorrelation of CA3 ensembles associated with contextual discrimination learning is impaired by Kv1.2 insufficiency

Hippocampus

2021 Dec 28

Eom, K;Lee, HR;Hyun, JH;An, H;Lee, YS;Ho, WK;Lee, SH;
PMID: 34964210 | DOI: 10.1002/hipo.23400

The associative network of hippocampal CA3 is thought to contribute to rapid formation of contextual memory from one-trial learning, but the network mechanisms underlying decorrelation of neuronal ensembles in CA3 is largely unknown. Kv1.2 expressions in rodent CA3 pyramidal cells (CA3-PCs) are polarized to distal apical dendrites, and its downregulation specifically enhances dendritic responses to perforant pathway (PP) synaptic inputs. We found that haploinsufficiency of Kv1.2 (Kcna2+/-) in CA3-PCs, but not Kv1.1 (Kcna1+/-), lowers the threshold for long-term potentiation (LTP) at PP-CA3 synapses, and that the Kcna2+/- mice are normal in discrimination of distinct contexts but impaired in discrimination of similar but slightly distinct contexts. We further examined the neuronal ensembles in CA3 and dentate gyrus (DG), which represent the two similar contexts using in situ hybridization of immediate early genes, Homer1a and Arc. The size and overlap of CA3 ensembles activated by the first visit to the similar contexts were not different between wild type and Kcna2+/- mice, but these ensemble parameters diverged over training days between genotypes, suggesting that abnormal plastic changes at PP-CA3 synapses of Kcna2+/- mice is responsible for the impaired pattern separation. Unlike CA3, DG ensembles were not different between two genotype mice. The DG ensembles were already separated on the first day, and their overlap did not further evolve. Eventually, the Kcna2+/- mice exhibited larger CA3 ensemble size and overlap upon retrieval of two contexts, compared to wild type or Kcna1+/- mice. These results suggest that sparse LTP at PP-CA3 synapse probably supervised by mossy fiber inputs is essential for gradual decorrelation of CA3 ensembles.

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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
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

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