scholarly journals Carbohydrate sulfation as a mechanism for fine-tuning Siglec ligands

2021 ◽  
Author(s):  
Jaesoo Jung ◽  
Jhon R Enterina ◽  
Duong T Bui ◽  
Fahima Mozaneh ◽  
Po-Han Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Survival Rates ◽  
Sodium Chlorate ◽  
Specific Pattern ◽  
Fine Tuning ◽  
General Mechanism ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Pharmacological Blockade

The immunomodulatory family of Siglecs recognize sialic acid-containing glycans as self, which is exploited in cancer for immune-evasion. The biochemical nature of Siglec ligands remains incompletely understood with emerging evidence suggesting the importance of carbohydrate sulfation. Here, we investigate how specific sulfate modifications affect Siglec ligands by overexpressing eight carbohydrate sulfotransferases (CHSTs) in five cell lines. Overexpression of three CHSTs (CHST1, CHST2, or CHST4) significantly enhances the binding of numerous Siglecs. Unexpectedly, two other CHSTs (Gal3ST2 and Gal3ST3) diminish Siglec binding, suggesting a new mode to modulate Siglec ligands via sulfation. Results are cell type dependent, indicating that the context in which sulfated glycans are presented is important. Moreover, pharmacological blockade of N- and O-glycan maturation reveals a cell type-specific pattern of importance for either class of glycan. Production of a highly homogenous CD33 (Siglec-3) fragment enabled a mass spectrometry-based binding assay to determine 10-fold and 3-fold enhanced affinity for Neu5Acα2-3(6-O-sulfo)Galβ1-4GlcNAc and Neu5Acα2-3Galβ1-4(6-O-sulfo)GlcNAc, respectively, over Neu5Acα2-3Galβ1-4GlcNAc. CD33 showed significant additivity in affinity (36-fold) for the disulfated ligand, Neu5Acα2-3(6-O-sulfo)Galβ1-4(6-O-sulfo)GlcNAc. Moreover, overexpression of both CHST1 and CHST2 in cells greatly enhanced the binding of several Siglecs, including CD33. Finally, we reveal that CHST1 is upregulated in numerous cancers, correlating with poorer survival rates and sodium chlorate sensitivity for the binding of Siglecs to cancer cell lines. These results provide new insights into carbohydrate sulfation as a modification that is a general mechanism for tuning Siglec ligands on cells, including in cancer.

Keratin polypeptides in the epidermis of the larval (ammocoete) sea lamprey, Petromyzon marinus L., show a cell type-specific immunolocalization

1994 ◽  
Vol 72 (1) ◽  
pp. 190-194 ◽  
Author(s):  
V. B. Alarcón ◽  
M. F. Filosa ◽  
J. H. Youson
Keyword(s):  
Petromyzon Marinus ◽  
Sea Lamprey ◽  
Specific Pattern ◽  
Immunofluorescent Staining ◽  
Cell Type ◽  
Keratin Polypeptides ◽  
A Cell ◽  
Positive Immunostaining ◽  
Cell Type Specific ◽  
Germinal Cells

Using immunofluorescent staining, the localization of keratin polypeptides in the epidermis of the larval (ammocoete) sea lamprey, Petromyzon marinus L., is described. Immunostaining with monoclonal antibodies against human keratin polypeptides showed that immunoreactivity was distributed in a cell type-specific pattern among the epidermal cells of ammocoete skin: immunoreactivity for keratin polypeptides Nos. 7 and 18 was prominent in skein and granular cells, respectively, while that for keratin polypeptide No. 19 was in cytoplasmic regions near the plasma membrane of both specialized (skein, granular, and mucous) and germinal cells. Positive immunostaining with a polyclonal antibody against bovine keratins suggests that there are other, as yet unidentified, keratin polypeptides in the epidermis. The significance of keratins as molecular markers of epidermal development is discussed.

scholarly journals Long Non-Coding RNA Expression Levels Modulate Cell-Type-Specific Splicing Patterns by Altering Their Interaction Landscape with RNA-Binding Proteins

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 593 ◽  
Author(s):  
Felipe Wendt Porto ◽  
Swapna Vidhur Daulatabad ◽  
Sarath Chandra Janga
Keyword(s):  
Alternative Splicing ◽  
Cell Lines ◽  
Rna Binding ◽  
Cell Type ◽  
Specific Manner ◽  
Alternatively Spliced ◽  
A Cell ◽  
Specific Alternative ◽  
Cell Type Specific ◽  
Rna Interaction

Recent developments in our understanding of the interactions between long non-coding RNAs (lncRNAs) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein–RNA interaction networks. Analysis of alternative splicing events across 39 lncRNA knockdown and wildtype RNA-sequencing datasets from three human cell lines—HeLa (cervical cancer), K562 (myeloid leukemia), and U87 (glioblastoma)—resulted in the high-confidence (false discovery rate (fdr) < 0.01) identification of 11,630 skipped exon events and 5895 retained intron events, implicating 759 genes to be impacted at the post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockdown were specific to the cell type. In tandem, the functions annotated to the genes affected by alternative splicing across each lncRNA knockdown also displayed cell-type specificity. To understand the mechanism behind this cell-type-specific alternative splicing pattern, we analyzed RNA-binding protein (RBP)–RNA interaction profiles across the spliced regions in order to observe cell-type-specific alternative splice event RBP binding preference. Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron–exon junctions in a cell-type-specific manner. The cellular functions affected by alternative splicing were also affected in a cell-type-specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs and their downstream functions. We propose that such lncRNA sponges can extensively rewire post-transcriptional gene regulatory networks by altering the protein–RNA interaction landscape in a cell-type-specific manner.

scholarly journals Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner

2005 ◽  
Vol 86 (8) ◽  
pp. 2305-2314 ◽  
Author(s):  
Marian Wiegand ◽  
Sascha Bossow ◽  
Wolfgang J. Neubert
Keyword(s):  
Cell Lines ◽  
Cytopathic Effect ◽  
Sendai Virus ◽  
Cellular Protein ◽  
Dependent Manner ◽  
Cell Type ◽  
Initiator Caspases ◽  
A Cell ◽  
Cell Type Specific ◽  
Intracellular Antigen

Induction of apoptosis during Sendai virus (SeV) infection has previously been documented to be triggered by initiator caspases (for strain F) or by a contribution of the cellular protein TIAR (T-cell-activated intracellular antigen-related) (for strain Z). Here, evidence was provided that both TIAR and caspases are simultaneously involved in apoptosis induction as a result of infection with SeV strain F. SeV F infection induced death in all tested cell lines, which could only be partially prevented through the pan-caspase inhibitor z-VAD-fmk. However, infection of seven different cell lines with the SeV mutant Fctr48z overexpressing a TIAR-sequestering RNA from the modified leader resulted in a cell type-dependent reduced cytopathic effect (CPE); in an earlier study a similar mutant derived from SeV Z was shown to prevent the induction of any CPE. Finally, blocking of caspases through z-VAD-fmk combined with Fctr48z infection led to complete abrogation of CPE, clearly demonstrating the existence of two separate mechanisms inducing cell death during SeV F infections. Interestingly, a cell type-specific interference between these two mechanisms could be detected during infection with the mutant virus Fctr48z: RNA transcribed from the mutated leader was able to trans-dominantly inhibit caspase-mediated apoptosis. Thus, virus-expressed factors enabling a well-balanced ratio of suppression and triggering of apoptosis seem to be essential for optimal virus replication.

scholarly journals Fine-tuning of epigenetic regulation with respect to promoter CpG content in a cell type-specific manner

Epigenetics ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. 747-759 ◽  
Author(s):  
Ruifang Li ◽  
Deepak Mav ◽  
Sara A Grimm ◽  
Raja Jothi ◽  
Ruchir Shah ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Fine Tuning ◽  
Cell Type ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific

IFIH1-deficiency results in a cell-type specific alteration of autophagic activity in response to S. typhimurium

2017 ◽  
Vol 55 (05) ◽  
pp. e28-e56
Author(s):  
S Macheiner ◽  
R Gerner ◽  
A Pfister ◽  
A Moschen ◽  
H Tilg
Keyword(s):  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Autophagic Activity ◽  
Specific Alteration

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific

Cytometric Profiling of CD133+ Cells in Human Colon Carcinoma Cell Lines Identifies a Common core Phenotype and Cell Type-specific Mosaics

2013 ◽  
Vol 28 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Marica Gemei ◽  
Rosa Di Noto ◽  
Peppino Mirabelli ◽  
Luigi Del Vecchio
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Cell Type ◽  
Carcinoma Cell Lines ◽  
Cell Type Specific

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.

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