Suppression of the METTL3-m6A-integrin ß1 axis by extracellular acidification impairs T cell infiltration and antitumor activity.

The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the "tumor acidity (TuAci) score" for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin ß1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy.

Invasive Ageratina adenophora can maintain its ecological advantages over time through releasing its autotoxicity by accumulating a bacterium Bacillus cereus.

Plant invasive success is attributed to invaders' ecological advantages over their native neighbors. However, increasing evidence suggests that these advantages are expected to attenuate over time because of natural enemy accumulation, ecological evolution of native species and autotoxicity. We determined how an invasive Ageratina adenophora could remain its competitive advantages over time by avoiding its autotoxicity. Our results highlighted that the autotoxicity of A. adenophora in its invaded soil was reduced by some microbes. Moreover, an autotoxic allelochemical, 2-coumaric acid glucoside, detected in the invaded soil, demonstrated distinctly autotoxic effects on its seed germination and seedling growth. However, the autotoxic effects were greatly alleviated by a bacterium Bacillus cereus, accumulated by A. adenophora. Furthermore, the allelochemical could be almost completely degraded by B. cereus within 96 h. Accordingly, we speculate that A. adenophora could aggregate B. cereus to release its autotoxicity maintaining its competitive advantages over time.

The latitudinal and longitudinal allelopathic patterns of an invasive alligator weed (Alternanthera philoxeroides) in China.

Allelopathy has been considered a good explanation for the successful invasion of some invasive plants. However, the real latitudinal and longitudinal allelopathic effects on native species have rarely been documented since many exotics have spread widely. We conducted a Petri dish experiment to determine the latitudinal and longitudinal allelopathic patterns of an invasive alligator weed (Alternanthera philoxeroides) on a common crop (Lactuca sativa) in China, and find what determines the allelopathic intensity. The results showed that the allelopathic effects of A. philoxeroides increased with the latitude while decreased with the longitude. This indicated that A. philoxeroides used its allelopathy to gain competitive advantages more in its recent invaded communities than that in its early invaded ones as A. philoxeroides is expanding from southeast China to northwest China. Furthermore, we found that the allelopathic intensity of A. philoxeroide was negatively correlated to the leaf contents of soluble carbohydrate (SC), carbon (C) and nitrogen (N), but that was positively correlated to the leaf contents of soluble protein (SP), free amino acids (FAA), plant polyphenol (PP), phosphorus (P) and potassium (K). These results suggested that the allelopathic intensity of A. philoxeroide was more determined by the limited P and K nutrients as well as the intermediate allelochemicals (SP, FAA, PP) rather than the unlimited C, N and SC. Thus, we can speculate that the negative or positive effects of plant aqueous extracts are a function of not only the extract concentrations but also the trade-offs between inhibition and promotion of all components in the extracts. Then we could reduce the allelopathic effects of A. philoxeroide by controlling the component contents in the plant tissues, by fertilization or other managements, especially in the plant recent invaded communities.

Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice.

BACKGROUND: In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW). METHOD: In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSCHpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSCHpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage. RESULTS: Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSCHpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSCHpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone. CONCLUSION: Our results demonstrated that Hpgds is required for wound healing, and ADSCHpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound.

Polyphyllin I alleviates lipopolysaccharide-induced inflammation reduces pyroptosis in BEAS-2B and HPAEC cells by inhibiting NF-κB signaling.

Polyphyllin I is an active steroidal saponin isolated from Paris polyphylla with anti-cancer and anti-inflammatory properties. The present study investigates the role of polyphyllin I in acute lung injury. Firstly, the human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were stimulated with increasing concentrations of lipopolysaccharide at 2, 5, and 10 µg/mL. The treatment with lipopolysaccharide reduced the cell viabilities of BEAS-2B and HPAEC, downregulated superoxide dismutase (SOD) and glutathione (GSH), and up-regulated myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the levels of TNF-α, IL-1ß, and IL-6 were also up-regulated in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Secondly, the lipopolysaccharide-treated cells were then incubated with different concentrations of polyphyllin I. Incubation with polyphyllin I enhanced the cell viabilities of lipopolysaccharide--treated BEAS-2B/HPAEC, up-regulated levels of SOD and GSH, and reduced MPO and MDA. Moreover, polyphyllin I reduced TNF-α, IL-1ß, and IL-6 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Thirdly, the up-regulation of GSDMD-N, pro-caspase-1, and cleaved caspase-1 proteins in lipopolysaccharide-treated BEAS-2B/HPAEC cells were decreased by polyphyllin I. Polyphyllin I increased the protein expression of GSDMD-D in the lipopolysaccharide-treated BEAS-2B/HPAEC cells, and inhibited the translocation of GSDMD from cytoplasm to plasma membrane. Lastly, polyphyllin I reduced the expression of p-p65 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. The over-expression of p65 counteracted with the inhibitory effects of polyphyllin I on oxidative stress and inflammation in lipopolysaccharide-treated BEAS-2B. In conclusion, polyphyllin I repressed the lipopolysaccharide-induced oxidative stress and inflammation in BEAS-2B and HPAEC, and reduced pyroptosis through inhibition of NF-κB signaling.

Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma.

Glioblastoma (GBM) is the deadliest primary brain tumor and is generally resistant to immunotherapy because of severe dysfunction of T cells. Novel treatment options are critically needed to overcome the immunotherapy resistance of GBM. Here we demonstrate that Zika virus (ZIKV) treatment improves the efficacy of anti-PD ligand 1 (PD-L1) immunotherapy in GBM. We found that ZIKV induces a strong pro-inflammatory response and increases CD4+ and CD8+ T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.

Insight into the Molecular Characteristics of Langhans Giant Cell by Combination of Laser Capture Microdissection and RNA Sequencing.

PURPOSE: The presence of Langhans giant cell (LGC) is a hallmark of mycobacterium-induced granuloma. The molecular characteristics and functions of LGC remain unclear to date. The study aimed to systematically characterize the molecular characteristics of LGC and reveal the potential functions. METHODS: Human LGCs were purified through laser capture microdissection (LCM) in vitro. RNA sequencing and in-depth transcriptome analysis were performed for purified LGCs and macrophages in the same system. Skin samples from mycobacterial infection patients were used to confirm some of the transcriptional expression. RESULTS: Human LGCs have different expression pattern from macrophages in the same in vitro system. A total of 967 differentially expressed genes were found. Bioinformatics analysis showed that LGCs are is characterized by active cell shape regulation, increased cytoskeletal components, weakened energy metabolism level, and reduced immune response. CCL7 may be a specific molecular for LGC to communicate with CCR1-expression cells in granuloma. CONCLUSION: LGCs have unique molecular characteristics different from that of macrophages. They may play a role in maintaining the hemostasis in granuloma.

Economic impact of powered stapler in video-assisted thoracic surgery lobectomy for lung Cancer in a Chinese tertiary hospital: a cost-minimization analysis.

BACKGROUND: To assess the economic impact of powered stapler use in video-assisted thoracic surgery (VATS) lobectomy for lung cancer in a Chinese tertiary care hospital. METHODS: This study identified 388 patients who received VATS lobectomy using the ECHELON powered stapler (n = 296) or the ECHELON manual stapler (n = 92) for lung cancer in a Chinese tertiary hospital. Multiple generalized linear regression analyses were conducted using data on hospital costs and patient characteristics to develop predictive equations for hospital costs in a cost-minimization analysis (CMA) model comparing hospital costs associated with the ECHELON powered stapler and the ECHELON manual stapler. CMA model was used to conduct scenario analysis to compare the ECHELON powered stapler with another manual stapler (Victor Medical). RESULTS: The multiple generalized linear regression analyses identified that using the ECHELON powered stapler in VATS lobectomy for lung cancer was associated with significantly lower drug costs than using the ECHELON manual stapler (coefficient - 0.256, 95% confidence interval: - 0.375 to - 0.139). The CMA model estimated that the ECHELON powered stapler could save hospital costs by ¥1653 when compared with the ECHELON manual stapler (¥65,531 vs. ¥67,184). The use of the ECHELON powered stapler also saved hospital costs by ¥4411 when compared with the Victor Medical manual stapler (¥65,531 vs. ¥69,942) in the scenario analysis. CONCLUSIONS: Compared to the two manual staplers used for VATS lobectomy for lung cancer in a Chinese tertiary hospital, the ECHELON powered stapler had 100% probability to save total hospital costs under present prices of the three staplers according to the CMA.

Arbuscular mycorrhizal fungi enhance nutrient acquisition and reduce aluminum toxicity in Lespedeza formosa under acid rain.

Lespedeza formosa is an economically important shrub in the agroecosystems of southern China, where acid rain (AR) is an increasingly serious environmental issue. However, the roles of arbuscular mycorrhizal fungi (AMF) in adapting the plants to AR stress are poorly understood. In this study, L. formosa seedlings were cultivated in a greenhouse, where the inoculated (colonization with Rhizophagus irregularis and Diversispora versiformis, alone and in combination) and non-inoculated plants were treated with three AR regimes (pH 5.6, 4.0, and 2.5) to evaluate the roles of AMF under acidic conditions. The results showed that AR individually suppressed plant growth by inhibiting photosynthetic parameters and induced Al phytotoxicity in non-mycorrhizal plants. However, mycorrhizal inoculation, especially in combination, significantly increased the total dry weight, photosynthetic capabilities, shoot nitrogen (N) concentration (average 15.8 and 16.7 mg g-1 for non-mycorrhizal and mycorrhizal plants, respectively) and plant phosphorus (P) concentration (average 1.6 and 2.3 mg g-1 for non-mycorrhizal and mycorrhizal plants, respectively) at pH 4.0, reduced N/P ratio (average 9.5 and 6.9 for non-mycorrhizal and mycorrhizal plants, respectively) at pH 4.0, and protected roots against Al phytotoxicity (average 2.0 and 1.4 mg g-1 for non-mycorrhizal and mycorrhizal roots, respectively), indicating that AMF could mitigate some of the detrimental effects of AR. Moreover, our findings suggest that AMF mainly benefited the plant through the combined effects of N concentrations and N/P ratios in shoots and Al3+ concentrations in roots under acidic conditions.

Transcriptome Analysis Reveals the Molecular Immunological Characteristics of Lesions in Patients with Halo Nevi When Compared to Stable Vitiligo, Normal Nevocytic Nevi and Cutaneous Melanoma.

BACKGROUND: Given their similar appearance and histology, halo nevi (HN) were considered as a type of vitiligo. However, whether HN have stronger immune response than stable vitiligo (VL) remains unclear. In addition, the molecular alterations in HN compared with normal nevocytic nevi (NN) and primary cutaneous melanoma (MM) must be determined. This study aimed to systematically characterize the molecular immunological features of HN. METHODS: Skin samples from patients with HN, VL, NN, and MM were obtained with informed consent. Each of the four groups underwent transcriptome sequencing and data analysis were for pairwise comparison. Quantitative real-time PCR (RT-qPCR) was conducted to confirm the transcriptional expression of some differentially expressed genes (DEGs) that were closely related to immunity. RESULTS: A total of 441 and 1507 DEGs were found in the HN/NN and HN/MM groups, respectively. Compared with those of VL, HN lesions contained 162 up-regulated DEGs and 12 down-regulated DEGs. Bioinformatics analysis showed that the up-regulated genes in HN were substantially enriched in immune response, immune deficiency, and immune rejection; biological stimulation (virus, bacteria); and proliferation and activation of immune cells. Immune cell composition analysis also confirmed high expression levels of multiple immunocytes in HN. CONCLUSION: The molecular immune mechanisms of HN and VL were similar, but the immune activity of HN was stronger than that of VL. Innate and adaptive immunity were involved in the pathogenesis and progression of HN and VL.

Clinical outcomes of powered and manual staplers in video-assisted thoracic surgery lobectomy for lung cancer.

Methods: This retrospective cohort study identified patients who underwent video-assisted thoracic surgery (VATS) lobectomy for lung cancer from January 2016 to December 2018 in a Chinese tertiary general hospital. The electronic hospital medical records associated with the VATS lobectomy for lung cancer were the data sources. Results: Based on the analysis of 433 patients with the utilization of staplers in their VATS lobectomy for lung cancer, using powered stapler was associated with significantly shorter operation time and postsurgery hospital stay length than using the manual stapler in the multivariable generalized linear regression analyses with the adjustment of patient characteristics. However, no other significant differences were observed for other clinical outcomes between the two staplers.

Identification and characterization of circRNAs encoded by MERS-CoV, SARS-CoV-1 and SARS-CoV-2.

The life-threatening coronaviruses MERS-CoV, SARS-CoV-1 and SARS-CoV-2 (SARS-CoV-1/2) have caused and will continue to cause enormous morbidity and mortality to humans. Virus-encoded noncoding RNAs are poorly understood in coronaviruses. Data mining of viral-infection-related RNA-sequencing data has resulted in the identification of 28 754, 720 and 3437 circRNAs encoded by MERS-CoV, SARS-CoV-1 and SARS-CoV-2, respectively. MERS-CoV exhibits much more prominent ability to encode circRNAs in all genomic regions than those of SARS-CoV-1/2. Viral circRNAs typically exhibit low expression levels. Moreover, majority of the viral circRNAs exhibit expressions only in the late stage of viral infection. Analysis of the competitive interactions of viral circRNAs, human miRNAs and mRNAs in MERS-CoV infections reveals that viral circRNAs up-regulated genes related to mRNA splicing and processing in the early stage of viral infection, and regulated genes involved in diverse functions including cancer, metabolism, autophagy, viral infection in the late stage of viral infection. Similar analysis in SARS-CoV-2 infections reveals that its viral circRNAs down-regulated genes associated with metabolic processes of cholesterol, alcohol, fatty acid and up-regulated genes associated with cellular responses to oxidative stress in the late stage of viral infection. A few genes regulated by viral circRNAs from both MERS-CoV and SARS-CoV-2 were enriched in several biological processes such as response to reactive oxygen and centrosome localization. This study provides the first glimpse into viral circRNAs in three deadly coronaviruses and would serve as a valuable resource for further studies of circRNAs in coronaviruses.

The m6A methylome of SARS-CoV-2 in host cells.

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically N6-methyladenosine (m6A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m6A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m6A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m6A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m6A methylome, exhibiting altered localization and motifs of m6A methylation in mRNAs. Altogether, our results identify m6A as a dynamic epitranscriptomic mark mediating the virus-host interaction.

Progress and challenge for computational quantification of tissue immune cells.

Tissue immune cells have long been recognized as important regulators for the maintenance of balance in the body system. Quantification of the abundance of different immune cells will provide enhanced understanding of the correlation between immune cells and normal or abnormal situations. Currently, computational methods to predict tissue immune cell compositions from bulk transcriptomes have been largely developed. Therefore, summarizing the advantages and disadvantages is appropriate. In addition, an examination of the challenges and possible solutions for these computational models will assist the development of this field. The common hypothesis of these models is that the expression of signature genes for immune cell types might represent the proportion of immune cells that contribute to the tissue transcriptome. In general, we grouped all reported tools into three groups, including reference-free, reference-based scoring and reference-based deconvolution methods. In this review, a summary of all the currently reported computational immune cell quantification tools and their applications, limitations, and perspectives are presented. Furthermore, some critical problems are found that have limited the performance and application of these models, including inadequate immune cell type, the collinearity problem, the impact of the tissue environment on the immune cell expression level, and the deficiency of standard datasets for model validation. To address these issues, tissue specific training datasets that include all known immune cells, a hierarchical computational framework, and benchmark datasets including both tissue expression profiles and the abundances of all the immune cells are proposed to further promote the development of this field.

Clinical and economic impact of oxidized regenerated cellulose for surgeries in a Chinese tertiary care hospital.

Aim: To assess the impact of oxidized regenerated cellulose (ORC) on blood transfusion and hospital costs associated with surgeries. Patients & methods: This retrospective cohort study selected ten surgeries to create propensity-score matching groups to compare ORC versus nonORC (conventional hemostatic techniques such as manual pressure, ligature and electrocautery). Results: NonORC was associated with both higher blood transfusion volume and higher hospital costs than ORC in endoscopic transnasal sphenoidal surgery, nonskull base craniotomy, hepatectomy, cholangiotomy, gastrectomy and lumbar surgery. However, nonORC was associated with better outcomes than ORC in open colorectal surgery, mammectomy and hip arthroplasty surgery. Conclusion: When compared with conventional hemostatic technique, using ORC could impact blood transfusion and hospital costs differently by surgical settings.

Cellular, Molecular, and Immunological Characteristics of Langhans Multinucleated Giant Cells Programmed by IL-15.

Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation (such as IFN-γ) induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs. Analysis of the IL-15‒treated adherent cell transcriptome identified gene networks for T cells, DNA damage and replication, and IFN-inducible genes that correlated with IL-15 treatment and LGC-type multinucleated giant cell formation. Gene networks enriched for myeloid cells were anticorrelated with IL-15 treatment and LGC formation. Functional studies revealed that T cells were required for IL-15‒induced LGC formation, involving a direct contact with myeloid cells through CD40L-CD40 interaction and IFN-γ release. These data indicate that IL-15 induces LGC formation through the direct interaction of activated T cells and myeloid cells.

Identification of dynamic signatures associated with smoking-related squamous cell lung cancer and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer. The aim of this study was to identify early diagnosis biomarkers for lung squamous cell carcinoma (SQCC) in COPD patients and to determine the potential pathogenetic mechanisms. The GSE12472 data set was downloaded from the Gene Expression Omnibus database. Differentially co-expressed links (DLs) and differentially expressed genes (DEGs) in both COPD and normal tissues, or in both SQCC + COPD and COPD samples were used to construct a dynamic network associated with high-risk genes for the SQCC pathogenetic process. Enrichment analysis was performed based on Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used the gene expression data and the clinical information to identify the co-expression modules based on weighted gene co-expression network analysis (WGCNA). In total, 205 dynamic DEGs, 5034 DLs and one pathway including CDKN1A, TP53, RB1 and MYC were found to have correlations with the pathogenetic progress. The pathogenetic mechanisms shared by both SQCC and COPD are closely related to oxidative stress, the immune response and infection. WGCNA identified 11 co-expression modules, where magenta and black were correlated with the "time to distant metastasis." And the "surgery due to" was closely related to the brown and blue modules. In conclusion, a pathway that includes TP53, CDKN1A, RB1 and MYC may play a vital role in driving COPD towards SQCC. Inflammatory processes and the immune response participate in COPD-related carcinogenesis.

Effects of radioactive 125I on apoptosis of HGC-27 gastric cancer cells.

Effects of radioactive 125I particles at different doses on apoptosis of HGC-27 gastric cancer cells were investigated. HGC-27 gastric cancer cell suspension was used to establish a tumor-bearing mouse model. The model was reared for approximately 3 weeks and then divided into the control group (implanted with blank particles), the low dose group (implanted with 1.48×10-7 Bq 125I particles), the medium dose group (implanted with 2.22×10-7 Bq 125I particles) and the high dose group (implanted with 2.96×10-7 Bq 125I particles) (n=15 per group). Six nude mice were randomly sacrificed to collect the tumor tissue and measure tumor volume and mass. TUNEL (TdT-mediated dUTP nick-end labeling) was used for detecting apoptosis of tumor cells, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detecting the relative expression of Bax, caspase-3 and caspase-8. On the 28th day after implantation, the apoptotic rate in the low, medium and high dose groups was significantly higher than that in the control group, which in the medium and high dose groups was significantly lower than that in the low dose group (P<0.05). On the 28th day after implantation, the relative expression of Bax, caspase-3 and caspase-8 mRNA in the control group was significantly lower than that in the low, medium and high dose groups (P<0.05), which in the low dose group was significantly higher than that in the medium and high dose groups (P<0.05). 125I particles can inhibit the growth of HGC-27 gastric cancer cell transplants and promote the expression of Bax, caspase-3 and caspase-8 mRNA in the tumor tissue. Low-dose 125I particles are significantly more effective than medium- or high-dose 125I particles.

seq-ImmuCC: Cell-Centric View of Tissue Transcriptome Measuring Cellular Compositions of Immune Microenvironment From Mouse RNA-Seq Data.

The RNA sequencing approach has been broadly used to provide gene-, pathway-, and network-centric analyses for various cell and tissue samples. However, thus far, rich cellular information carried in tissue samples has not been thoroughly characterized from RNA-Seq data. Therefore, it would expand our horizons to better understand the biological processes of the body by incorporating a cell-centric view of tissue transcriptome. Here, a computational model named seq-ImmuCC was developed to infer the relative proportions of 10 major immune cells in mouse tissues from RNA-Seq data. The performance of seq-ImmuCC was evaluated among multiple computational algorithms, transcriptional platforms, and simulated and experimental datasets. The test results showed its stable performance and superb consistency with experimental observations under different conditions. With seq-ImmuCC, we generated the comprehensive landscape of immune cell compositions in 27 normal mouse tissues and extracted the distinct signatures of immune cell proportion among various tissue types. Furthermore, we quantitatively characterized and compared 18 different types of mouse tumor tissues of distinct cell origins with their immune cell compositions, which provided a comprehensive and informative measurement for the immune microenvironment inside tumor tissues. The online server of seq-ImmuCC are freely available at http://wap-lab.org:3200/immune/.