scholarly journals Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons

2016 ◽  
Vol 113 (35) ◽  
pp. E5222-E5231 ◽  
Author(s):  
Csaba Földy ◽  
Spyros Darmanis ◽  
Jason Aoto ◽  
Robert C. Malenka ◽  
Stephen R. Quake ◽  
...  

In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1213
Author(s):  
Cian D’Arcy ◽  
Christina Kiel

Cell adhesion molecules (CAMs) of the cadherin, integrin, immunoglobulin, and selectin protein families are indispensable for the formation and maintenance of multicellular tissues, especially epithelia. In the epidermis, they are involved in cell–cell contacts and in cellular interactions with the extracellular matrix (ECM), thereby contributing to the structural integrity and barrier formation of the skin. Bulk and single cell RNA sequencing data show that >170 CAMs are expressed in the healthy human skin, with high expression levels in melanocytes, keratinocytes, endothelial, and smooth muscle cells. Alterations in expression levels of CAMs are involved in melanoma propagation, interaction with the microenvironment, and metastasis. Recent mechanistic analyses together with protein and gene expression data provide a better picture of the role of CAMs in the context of skin physiology and melanoma. Here, we review progress in the field and discuss molecular mechanisms in light of gene expression profiles, including recent single cell RNA expression information. We highlight key adhesion molecules in melanoma, which can guide the identification of pathways and strategies for novel anti-melanoma therapies.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiayu Shen ◽  
Shuqian Yu ◽  
Xiwen Sun ◽  
Meichen Yin ◽  
Jing Fei ◽  
...  

Abstract Background Ovarian cancer (OC) is the deadliest cause in the gynecological malignancies. Most OC patients are diagnosed in advanced stages with less than 40% of women cured. However, the possible mechanism underlying tumorigenesis and candidate biomarkers remain to be further elucidated. Results Gene expression profiles of GSE18520, GSE54388, and GSE27651 were available from Gene Expression Omnibus (GEO) database with a total of 91 OC samples and 22 normal ovarian (OV) tissues. Three hundred forty-nine differentially expressed genes (DEGs) were screened between OC tissues and OV tissues via GEO2R and online Venn software, followed by KEGG pathway and gene ontology (GO) enrichment analysis. The enriched functions and pathways of these DEGs contain male gonad development, cellular response to transforming growth factor beta stimulus, positive regulation of transcription from RNA polymerase II promoter, calcium independent cell-cell adhesion via plasma membrane cell adhesion molecules, extracellular matrix organization, pathways in cancer, cell cycle, cell adhesion molecules, PI3K-AKT signaling pathway, and progesterone mediated oocyte maturation. The protein-protein network (PPI) was established and module analysis was carried out using STRING and Cytoscape. Next, with PPI network analyzed by four topological methods in Cytohubba plugin of Cytoscape, 6 overlapping genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) were eventually selected. GEPIA and Oncomine were implemented for validating the gene expression and all the six hub genes were highly expressed in OC specimens compared to normal OV tissues. Furthermore, 5 of 6 genes except for DTL were associated with worse prognosis using Kaplan Meier-plotter online tool and 3 of 6 genes were significantly related to clinical stages, including RRM2, DTL, and KIF15. Additionally, cBioPortal showed that TOP2A and RRM2 were the targets of cancer drugs in patients with OC, indicating the other four genes may also be potential drug targets. Conclusion Six hub genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) present promising predictive value for the development and prognosis of OC and may be used as candidate targets for diagnosis and treatment of OC.


1993 ◽  
Vol 44 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Etienne J. Nouwen ◽  
Simonne Dauwe ◽  
Inge Van Der Biest ◽  
Marc E. De Broe

2007 ◽  
Vol 367 (4) ◽  
pp. 996-1006 ◽  
Author(s):  
Yoshikazu Tsukasaki ◽  
Kazuo Kitamura ◽  
Kazuya Shimizu ◽  
Atsuko H. Iwane ◽  
Yoshimi Takai ◽  
...  

Author(s):  
Toomas Jagomäe ◽  
Katyayani Singh ◽  
Mari-Anne Philips ◽  
Mohan Jayaram ◽  
Kadri Seppa ◽  
...  

The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders. Usage of alternative promoter-specific 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms and Negr1, in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, 13.5, 17; post natal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders.


2015 ◽  
Vol 6 ◽  
pp. 157-166 ◽  
Author(s):  
Miao Yu ◽  
Nico Strohmeyer ◽  
Jinghe Wang ◽  
Daniel J Müller ◽  
Jonne Helenius

Mammalian cells regulate adhesion by expressing and regulating a diverse array of cell adhesion molecules on their cell surfaces. Since different cell types express distinct sets of cell adhesion molecules, substrate-specific adhesion is cell type- and condition-dependent. Single-cell force spectroscopy is used to quantify the contribution of cell adhesion molecules to adhesion of cells to specific substrates at both the cell and single molecule level. However, the low throughput of single-cell adhesion experiments greatly limits the number of substrates that can be examined. In order to overcome this limitation, segmented polydimethylsiloxane (PDMS) masks were developed, allowing the measurement of cell adhesion to multiple substrates. To verify the utility of the masks, the adhesion of four different cell lines, HeLa (Kyoto), prostate cancer (PC), mouse kidney fibroblast and MDCK, to three extracellular matrix proteins, fibronectin, collagen I and laminin 332, was examined. The adhesion of each cell line to different matrix proteins was found to be distinct; no two cell lines adhered equally to each of the proteins. The PDMS masks improved the throughput limitation of single-cell force spectroscopy and allowed for experiments that previously were not feasible. Since the masks are economical and versatile, they can aid in the improvement of various assays.


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