{"title":"Commentary on \"Antigen Retrieval Immunohistochemistry: Past, Present, and Future\".","authors":"Clive R Taylor, Shan-Rong Shi","doi":"10.1369/00221554221147086","DOIUrl":"10.1369/00221554221147086","url":null,"abstract":"Almost half a century has passed from the first successful application of peroxidase labeled antibodies to routinely processed formalin-fixed paraffin-embedded (FFPE) tissues with the express purpose of improved diagnosis. Retention of the morphological features that are the foundation of surgical pathology was key to rendering the “immunoperoxidase” method attractive for diagnostic use. However, significant obstacles remained, including the limited number of antibodies that “worked” on FFPE tissues, the relatively low sensitivity of detection methods, and, most important in terms of broad utility, the deleterious effects of formalin fixation on many antigens. There were advances, some dramatic, but overall progress was slow.1 The advent of the hybridoma technique was eventually to lead to the generation of numerous monoclonal antibodies that were rapidly incorporated into immunohistochemistry. Concurrently, detection systems improved, and attempts were made to “undo” the effects of formalin fixation by enzymatic digestion, with limited success. Against this background, the introduction of what now is known as “antigen retrieval” (AR), or by some as heat induced epitope retrieval (HIER), provided huge impetus to the field, having the effect of greatly increasing the number of antigens that were demonstrable in FFPE tissues, including many with diagnostic application. This advance was entirely counterintuitive and was based upon exhaustive research in dusty libraries (no Internet searches!). There evidence was found that the “antigenic potency” of tetanus toxoid, toxin that had been inactivated by formalin, could in large part be restored by something as simple as boiling. Why not apply the same approach to FFPE tissues? The current issue of the Journal of Histochemistry & Cytochemistry has selected as its Classical Article a paper by Shan-Rong Shi, Richard Cote, and Clive Taylor that describes the evolution of the AR method, and the impact of AR in diagnostic pathology and broader fields of research, as measured just 5 years after its introduction. That this initial promise has been fulfilled manyfold is attested by extensive day-to-day use of AR in histochemistry laboratories worldwide, and by an enormous ever expanding literature, even providing the basis for DNA extraction methods that 1147086 JHCXXX10.1369/00221554221147086Antigen Retrieval: A Simple Idea With Major Ongoing ImpactTaylor and Shi article-commentary2022","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 11-12","pages":"769-770"},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10714434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on \"Application of Photoshop-based Image Analysis to Quantification of Hormone Receptor Expression in Breast Cancer\".","authors":"Allen M Gown","doi":"10.1369/00221554221145227","DOIUrl":"10.1369/00221554221145227","url":null,"abstract":"At the time of publication of this article, image analysis as applied to diagnostic surgical pathology was a nascent technology, often characterized as a “solution in search of a problem.” After all, biomarkers such as estrogen receptor (ER) in breast cancer were scored in a threshold manner, with the assumption that this scoring was highly accurate and reproducible. Unfortunately, several studies in the early 2000s found significant discordance in this ER evaluation when slides were re-reviewed.1,2 Ironically, prior approaches to determining ER expression in breast cancer, for example, the dextran-coated charcoal method, were quantifiable and reproducible, but required fresh frozen tissue and could not be used on formalin-fixed paraffin-embedded tissue. Image analysis on deparaffinized, formalin-fixed tissue sections immunostained with appropriate antibodies was anticipated to be a method that could increase the predictive power of IHC determination of hormone receptor status. Indeed, this 1997 paper was one of the first to employ image analysis in the evaluation of ER. While after more than two decades Photoshop has maintained its role as a premier raster graphics and digital art editor, it has not taken a second life as an image analysis tool. We selected Photoshop as a “maverick” technique that permitted us to accomplish the analysis we desired, but to also avoid the use of commercial image analysis instruments and software, which at that time were expensive and unaffordable for our laboratory. Today, while commercial image analysis hardware and software are legion, free public domain software such as QuPath can yield comparable results as many commercial software packages3 and far exceed the capabilities of Photoshop. While our 1997 paper succeeded as a “proof of principle,” now 25 years later, ER is still not quantified in the vast majority of cases, but is instead still “eyeballed” to determine whether more than 1% of tumor cells are positive for nuclear signal (or between 1% and 10%), but no image analysis–based quantification is required.4 There may still be a role in the future for more quantitative ER determination in breast cancer, but that will be determined not by technology alone but largely by evidence that may be forthcoming from clinical studies. But it will almost certainly not involve the use of Photoshop!","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 11-12","pages":"767-768"},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long Hanging Structure of Collagen VII Connects the Elastic Fibers and the Basement Membrane in Young Skin Tissue.","authors":"Takeshi Tohgasaki, Shino Nishizawa, Shinya Kondo, Shioji Ishiwatari, Tetsuhito Sakurai","doi":"10.1369/00221554221145998","DOIUrl":"10.1369/00221554221145998","url":null,"abstract":"<p><p>Aging leads to substantial structural changes in the skin. Elastic fibers maintain skin structure, but their degeneration and loss of function with age result in wrinkle formation and loss of skin elasticity. Oxytalan fiber, a type of elastic fiber, extends close to the dermal-epidermal junction (DEJ) from the back of the dermis. Oxytalan fibers are abundant in the papillary layer and contribute to skin elasticity and texture. However, to accurately understand the mechanisms of skin elasticity, the interaction between elastic fibers and DEJ should be elucidated. Here, we investigated elastic fibers and DEJ and their structural alterations with aging. Several basement membrane proteins [collagen (COL) IV, COLVII, and laminin 332], fibrous tropoelastin, and fibrillin-1 in excised human skin tissue were observed using three-dimensional imaging. Age-related alterations in COLVII, elastic fibers, and fibrillin-1 were evaluated. We found that COLVII forms long hanging structures and is co-localized with fibrous tropoelastin in young skin but not aged skin. Fibrillin-1-rich regions were observed at the tips of elastin fibers in young skin tissue, but rarely in aged skin. This co-localization of elastic fiber and COLVII may maintain skin structure, thereby preventing wrinkling and sagging. COLVII is a potential therapeutic target for skin wrinkling.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 11-12","pages":"751-757"},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abnormal Expression of an Insulin Synthesizing Enzyme in Islets of Adult Autoantibody Positive Donors.","authors":"Gladys Teitelman","doi":"10.1369/00221554221138368","DOIUrl":"10.1369/00221554221138368","url":null,"abstract":"<p><p>The observation that the two active forms of proprotein convertase 1/3 (PC1/3) were differentially expressed in beta cells of normal islets raised the possibility that this heterogeneity is lost during type 1 diabetes (T1D) progression. To test this hypothesis, the expression of the convertase was evaluated by confocal microscopy in sections of human pancreas of autoantibody positive (AA+) and T1D donors and compared with that of control. Islets of T1D pancreas were comprised of beta cells expressing either low or high PC1/3 levels and all islets of a pancreatic section contained only one beta cell type. Pancreata of AA+ donors contained either of these two classes of islets intermixed with normal islets comprised of beta cells with heterogeneous PC1/3 expression. This alteration affected the expression of proinsulin and insulin, which in most AA+ and T1D donors were lower than in controls. The present results indicate that the heterogeneity of PC1/3 expression is lost in all beta cells in a subset islets of AA+ donors and in all islets of T1D donors. These findings suggest that the heterogeneity of PC1/3 expression is a biomarker of human beta cell health and that its loss coincides with the initial stages of T1D.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 10","pages":"695-706"},"PeriodicalIF":3.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660365/pdf/10.1369_00221554221138368.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9493247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aberrant Expression of Thymosin Beta-4 Correlates With Advanced Disease and BRAF V600E Mutation in Thyroid Cancer.","authors":"Chi-Yu Kuo, Jie-Yang Jhuang, Wen-Chien Huang, Shih-Ping Cheng","doi":"10.1369/00221554221138370","DOIUrl":"10.1369/00221554221138370","url":null,"abstract":"<p><p>Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 10","pages":"707-716"},"PeriodicalIF":3.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660367/pdf/10.1369_00221554221138370.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donald J Johann, Ik Jae Shin, Adam Roberge, Sarah Laun, Erich A Peterson, Meei Liu, Matthew A Steliga, Jason Muesse, Michael R Emmert-Buck, Michael A Tangrea
{"title":"Effect of Antigen Retrieval on Genomic DNA From Immunodissected Samples.","authors":"Donald J Johann, Ik Jae Shin, Adam Roberge, Sarah Laun, Erich A Peterson, Meei Liu, Matthew A Steliga, Jason Muesse, Michael R Emmert-Buck, Michael A Tangrea","doi":"10.1369/00221554221124163","DOIUrl":"https://doi.org/10.1369/00221554221124163","url":null,"abstract":"<p><p>Immunohistochemical (IHC) staining is an established technique for visualizing proteins in tissue sections for research studies and clinical applications. IHC is increasingly used as a targeting strategy for procurement of labeled cells via tissue microdissection, including immunodissection, computer-aided laser dissection (CALD), expression microdissection (xMD), and other techniques. The initial antigen retrieval (AR) process increases epitope availability and improves staining characteristics; however, the procedure can damage DNA. To better understand the effects of AR on DNA quality and quantity in immunodissected samples, both clinical specimens (<i>KRAS</i> gene mutation positive cases) and model system samples (lung cancer patient-derived xenograft tissue) were subjected to commonly employed AR methods (heat induced epitope retrieval [HIER], protease digestion) and the effects on DNA were assessed by Qubit, fragment analysis, quantitative PCR, digital droplet PCR (ddPCR), library preparation, and targeted sequencing. The data showed that HIER resulted in optimal IHC staining characteristics, but induced significant damage to DNA, producing extensive fragmentation and decreased overall yields. However, neither of the AR methods combined with IHC prevented ddPCR amplification of small amplicons and gene mutations were successfully identified from immunodissected clinical samples. The results indicate for the first time that DNA recovered from immunostained slides after standard AR and IHC processing can be successfully employed for genomic mutation analysis via ddPCR and next-generation sequencing (NGS) short-read methods.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 9","pages":"643-658"},"PeriodicalIF":3.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527476/pdf/10.1369_00221554221124163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harim Tavares Dos Santos, Kihoon Nam, Frank M Maslow, Travis Small, Tabitha L I Galloway, Laura M Dooley, Patrick T Tassone, Robert P Zitsch, Gary A Weisman, Olga J Baker
{"title":"Tuft Cells Are Present in Submandibular Glands Across Species.","authors":"Harim Tavares Dos Santos, Kihoon Nam, Frank M Maslow, Travis Small, Tabitha L I Galloway, Laura M Dooley, Patrick T Tassone, Robert P Zitsch, Gary A Weisman, Olga J Baker","doi":"10.1369/00221554221120301","DOIUrl":"10.1369/00221554221120301","url":null,"abstract":"<p><p>Tuft cells are bottle-shaped, microvilli-projecting chemosensory cells located in the lining of a variety of epithelial tissues and, following their identification approximately 60 years ago, have been linked to immune system function in a variety of epithelia. Until recently, Tuft cells had not been convincingly demonstrated to be present in salivary glands with their detection by transmission electron microscopy only shown in a handful of earlier studies using rat salivary glands, and no follow-up work has been conducted to verify their presence in salivary glands of other species. Here, we demonstrate that Tuft cells are present in the submandibular glands of various species (i.e., mouse, pig and human) using transmission electron microscopy and confocal immunofluorescent analysis for the POU class 2 homeobox 3 (POU2F3), which is considered to be a master regulator of Tuft cell identity.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 9","pages":"659-667"},"PeriodicalIF":1.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527474/pdf/10.1369_00221554221120301.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10133735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Denis Depes, Ari Mennander, Rauha Vehniäinen, Timo Paavonen, Ivana Kholová
{"title":"Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality.","authors":"Denis Depes, Ari Mennander, Rauha Vehniäinen, Timo Paavonen, Ivana Kholová","doi":"10.1369/00221554221129899","DOIUrl":"https://doi.org/10.1369/00221554221129899","url":null,"abstract":"<p><p>Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm<sup>2</sup>/mm<sup>2</sup>, <i>p</i>=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm<sup>2</sup>/mm<sup>2</sup>) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (<i>p</i>=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 9","pages":"627-642"},"PeriodicalIF":3.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527475/pdf/10.1369_00221554221129899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatially Resolved and Highly Multiplexed Protein and RNA In Situ Detection by Combining CODEX With RNAscope In Situ Hybridization.","authors":"Yilun Cheng, Rachel K Burrack, Qingsheng Li","doi":"10.1369/00221554221114174","DOIUrl":"https://doi.org/10.1369/00221554221114174","url":null,"abstract":"<p><p>Highly multiplexed protein and RNA in situ detection on a single tissue section concurrently is highly desirable for both basic and applied biomedical research. CO-detection by inDEXing (CODEX) is a new and powerful platform to visualize up to 60 protein biomarkers in situ, and RNAscope in situ hybridization (RNAscope) is a novel RNA detection system with high sensitivity and unprecedent specificity at a single-cell level. Nevertheless, to our knowledge, the combination of CODEX and RNAscope remained unreported until this study. Here, we report a simple and reproducible combination of CODEX and RNAscope. We also determined the cross-reactivities of CODEX anti-human antibodies to rhesus macaques, a widely used animal model of human disease.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 8","pages":"571-581"},"PeriodicalIF":3.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393509/pdf/10.1369_00221554221114174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esmeralda K Bosma, Shahan Darwesh, Jia Y Zheng, Cornelis J F van Noorden, Reinier O Schlingemann, Ingeborg Klaassen
{"title":"Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells.","authors":"Esmeralda K Bosma, Shahan Darwesh, Jia Y Zheng, Cornelis J F van Noorden, Reinier O Schlingemann, Ingeborg Klaassen","doi":"10.1369/00221554221115767","DOIUrl":"https://doi.org/10.1369/00221554221115767","url":null,"abstract":"<p><p>Endothelial cells (ECs) form a precisely regulated polarized monolayer in capillary walls. Vascular endothelial growth factor-A (VEGF-A) induces endothelial hyperpermeability, and VEGF-A applied to the basolateral side, but not the apical side, has been shown to be a strong barrier disruptor in blood-retinal barrier ECs. We show here that VEGF-A presented to the basolateral side of human umbilical vein ECs (HUVECs) induces higher permeability than apical stimulation, which is similar to results obtained with bovine retinal ECs. We investigated with immunocytochemistry and confocal imaging the distribution of VEGF receptor-2 (VEGFR2) and neuropilin-2 (NRP2) in perinuclear apical and basolateral membrane domains. Orthogonal z-sections of cultured HUVECs were obtained, and the fluorescence intensity at the apical and basolateral membrane compartments was measured. We found that VEGFR2 and NRP2 are evenly distributed throughout perinuclear apical and basolateral membrane compartments in unstimulated HUVECs grown on Transwell inserts, whereas basolateral VEGF-A stimulation induces a shift toward basolateral VEGFR2 and NRP2 localization. When HUVECs were grown on coverslips, the distribution of VEGFR2 and NRP2 across the perinuclear apical and basolateral membrane domains was different. Our findings demonstrate that HUVECs dynamically regulate VEGFR2 and NRP2 localization on membrane microdomains, depending on growth conditions and the polarity of VEGF-A stimulation.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 8","pages":"557-569"},"PeriodicalIF":3.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393510/pdf/10.1369_00221554221115767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}