Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system

Tubau-Juni, Nuria; Bassaganya‐Riera, Josep; Leber, Andrew; Zoccoli-Rodriguez, Victoria; Kronsteiner, Barbara; Viladomiu, Monica; Abedi, Vida; Philipson, Casandra; Hontecillas, Raquel

doi:10.1038/s41598-020-68439-8

Cited by 10 publications

(12 citation statements)

References 67 publications

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“…The function of our key gene in EMT may indicate that PLXDC2 is a regulator of tumor metastasis. It has also been reported that deficiency of PLXDC2 suppresses the bacterial colonization of HP infection (Tubau-Juni et al, 2020). In our studies, however, we discovered no clear evidence that the expression level of PLXDC2 may influence HP infection in GC (Supplementary Figure 2).…”

Section: Discussioncontrasting

confidence: 75%

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Guan

Wang

et al. 2021

Front. Cell Dev. Biol.

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The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2’s correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.

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Section: Discussioncontrasting

confidence: 75%

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Guan

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…S4A). Genes upregulated in Fb MME include Lama2 (loss is associated with muscular dystrophy ( 39 )), Plxdc2 (inflammation suppressor ( 40 )), and Cxcl14 , (implicated in chemotaxis ( 41 )). Downregulated genes in e23AON-treated mdx Fb MME include Sparc, Meg3 and collagens, Col3a1, Col1a1 , and Col1a2 , which have been implicated in inflammation or fibrosis (Datafile S3, Table S1d, Fig.…”

Section: Resultsmentioning

confidence: 99%

Single nuclei transcriptomics of muscle reveals intra-muscular cell dynamics linked to dystrophin loss and rescue

Scripture-Adams

Chesmore

Barthélémy

et al. 2022

Preprint

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In Duchenne muscular dystrophy, dystrophin loss leads to chronic muscle damage, dysregulation of repair, fibro-fatty replacement, and weakness. We develop methodology to efficiently isolate individual nuclei from frozen skeletal muscle, allowing single nuclei sequencing of irreplaceable archival samples from small samples. We apply this method to identify cell and gene expression dynamics within human DMD and mdx mouse muscle, characterizing treatment effects of dystrophin rescue by exon skipping therapy at single nuclei resolution. DMD exon 23 skipping events are directly observed and increased in myonuclei from treated mice. We describe partial rescue of type IIa and IIx myofibers, expansion of a novel MDSC-like myeloid population, recovery of repair/remodeling M2- macrophage, and repression of inflammatory POSTN1+ fibroblasts in response to exon skipping and partial dystrophin restoration. Use of this method enables exploration of cellular and transcriptomic mechanisms of dystrophin loss and repair.

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“…Host colonization, tolerance induction, and induction of immunoregulatory response require the role of the macrophage peroxisome proliferator-activated receptor gamma (PPARγ), an anti-inflammatory transcription factor [ 45 ]. These results suggest that Hp might represent a suitable system to identify the regulatory mechanisms controlling the host immune response [ 46 ].…”

Section: Potential Role Of Hp Against Inflammamentioning

confidence: 99%

“…In vitro cocultures of a wild type or of PPARγ-deficient bone-marrow-derived macrophages with live Hp identified several potential new immunoregulatory genes. One of them (Plexin domain-containing 2; Plxdc2 ) was confirmed to play an immunoregulatory role in the Hp infection, in a mouse model of inflammatory bowel disease, and potentially in other inflammatory and autoimmune diseases [ 46 ].…”

Section: Potential Role Of Hp Against Inflammamentioning

confidence: 99%

Genetics of Host Protection against Helicobacter pylori Infections

Capparelli

Iannelli

2021

IJMS

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This narrative review discusses the genetics of protection against Helicobacter pylori (Hp) infection. After a brief overview of the importance of studying infectious disease genes, we provide a detailed account of the properties of Hp, with a view to those relevant for our topic. Hp displays a very high level of genetic diversity, detectable even between single colonies from the same patient. The high genetic diversity of Hp can be evaded by stratifying patients according to the infecting Hp strain. This approach enhances the power and replication of the study. Scanning for single nucleotide polymorphisms is generally not successful since genes rarely work alone. We suggest selecting genes to study from among members of the same family, which are therefore inclined to cooperate. Further, extending the analysis to the metabolism would significantly enhance the power of the study. This combined approach displays the protective role of MyD88, TIRAP, and IL1RL1 against Hp infection. Finally, several studies in humans have demonstrated that the blood T cell levels are under the genetic control of the CD39+ T regulatory cells (TREGS).

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Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system

Cited by 10 publications

References 67 publications

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer

Single nuclei transcriptomics of muscle reveals intra-muscular cell dynamics linked to dystrophin loss and rescue

Genetics of Host Protection against Helicobacter pylori Infections

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