Transcriptome profiling reveals target in primary myelofibrosis together with structural biology study on novel natural inhibitors regarding JAK2

Li, Weihang; Yuan, Bin; Zhao, Yingjing; Lu, Tianxing; Zhang, Shilei; Ding, Ziyi; Wang, Dong; Zhong, Sheng; Gao, Guangxun; Yan, Ming

doi:10.18632/aging.202635

Cited by 9 publications

(5 citation statements)

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“…WGCNA is a powerful holistic research tool for data mining, the mathematical theory was firstly proposed in 2005 ( Zhang and Horvath, 2005 ), and the applications of WGCNA together with microarray technology have been witnessed widely in recent years in various tumor or non-tumor diseases, including primary myelofibrosis, osteosarcoma, gastric cancer, chronic obstructive pulmonary disease, etc. ( Li et al, 2021a ; Li et al, 2021b ; Chen et al, 2021 ; Li et al, 2021c ; Deng et al, 2021 ). In a nutshell, WGCNA builds a bridge between sample characteristics and gene expression profiles, which was performed in this study, together with other analytical methods.…”

Section: Discussionmentioning

confidence: 99%

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD

Ding

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Objectives: Intervertebral disc degeneration is a progressive and chronic disease, usually manifesting as low back pain. This study aimed to screen effective biomarkers for medical practice as well as figuring out immune infiltration situations between circulation and intervertebral discs.Methods: Gene expression profiles of GSE124272 was included for differentially analysis, WGCNA and immune infiltration analysis from GEO database, and other GSE series were used as validation datasets. A series of validation methods were conducted to verify the robustness of hub genes, such as principal component analysis, machine learning models, and expression verification. Lastly, nomogram was established for medical practice.Results: 10 genes were commonly screened via combination of DEGs, WGCNA analysis and lipid metabolism related genes. Furthermore, 3 hub gens CYP27A1, FAR2, CYP1B1 were chosen for subsequent analysis based on validation of different methods. GSEA analysis discovered that neutrophil extracellular traps formation and NOD-like receptor signaling pathway was activated during IDD. Immune infiltration analysis demonstrated that the imbalance of neutrophils and γδT cells were significantly correlated with IDD progression. Nomogram was established based on CYP27A1, FAR2, CYP1B1 and age, the calibration plot confirmed the stability of our model.Conclusion: CYP27A1, FAR2, CYP1B1 were considered as hub lipid metabolism related genes (LMRGs) in the development of IDD, which were regarded as candidate diagnostic biomarkers especially in circulation. The effects are worth expected in the early diagnosis of IDD through detecting these genes in blood.

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Section: Discussionmentioning

confidence: 99%

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD

Ding

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…MCODE algorithm was used for clustering given network links based on topology to identify densely connected subgroups. MCODE scores and P values were calculated and fully assessed to screen the most correlated subgroup; ‘Cytohubba’ algorithm provided 11 different topological methods including ‘Betweenness’, ‘BottleNeck’, ‘Closeness’, ‘Degree’, ‘DMNC’, ‘EcCentricity’, ‘EPC’, ‘MCC’, ‘MNC’, ‘Radiality’, ‘Stress’, which applied for identifying key targets from a complex network, thus, hub genes were identified and fully estimated by each algorithm in ‘cytohubba’, the most correlated genes appeared in each algorithm were finally determined as hub genes ( 22 ).…”

Section: Methodsmentioning

confidence: 99%

Revealing the Key MSCs Niches and Pathogenic Genes in Influencing CEP Homeostasis: A Conjoint Analysis of Single-Cell and WGCNA

Zhang

Zhao

et al. 2022

Front. Immunol.

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Degenerative disc disease (DDD), a major contributor to discogenic pain, which is mainly resulted from the dysfunction of nucleus pulposus (NP), annulus fibrosis (AF) and cartilage endplate (CEP) cells. Genetic and cellular components alterations in CEP may influence disc homeostasis, while few single-cell RNA sequencing (scRNA-seq) report in CEP makes it a challenge to evaluate cellular heterogeneity in CEP. Here, this study conducted a first conjoint analysis of weighted gene co-expression network analysis (WGCNA) and scRNA-seq in CEP, systematically analyzed the interested module, immune infiltration situation, and cell niches in CEP. WGCNA and protein-protein interaction (PPI) network determined a group of gene signatures responsible for degenerative CEP, including BRD4, RAF1, ANGPT1, CHD7 and NOP56; differentially immune analysis elucidated that CD4+ T cells, NK cells and dendritic cells were highly activated in degenerative CEP; then single-cell resolution transcriptomic landscape further identified several mesenchymal stem cells and other cellular components focused on human CEP, which illuminated niche atlas of different cell subpopulations: 8 populations were identified by distinct molecular signatures. Among which, NP progenitor/mesenchymal stem cells (NPMSC), also served as multipotent stem cells in CEP, exhibited regenerative and therapeutic potentials in promoting bone repair and maintaining bone homeostasis through SPP1, NRP1-related cascade reactions; regulatory and effector mesenchymal chondrocytes could be further classified into 2 different subtypes, and each subtype behaved potential opposite effects in maintaining cartilage homeostasis; next, the potential functional differences of each mesenchymal stem cell populations and the possible interactions with different cell types analysis revealed that JAG1, SPP1, MIF and PDGF etc. generated by different cells could regulate the CEP homeostasis by bone formation or angiogenesis, which could be served as novel therapeutic targets for degenerative CEP. In brief, this study mainly revealed the mesenchymal stem cells populations complexity and phenotypic characteristics in CEP. In brief, this study filled the gap in the knowledge of CEP components, further enhanced researchers’ understanding of CEP and their cell niches constitution.

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“…In recent years, with the rapid development of HTS technology together with bioinformatics, it has been widely applied to study the occurrence and development of diseases and further analyze the disease-related causative genes and their biological significance [ 17 – 19 ]. Besides, the novel drug screening based on hub genes has also been reported [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Reveals CXCR4 and IGF1 Behave Different Roles in Weightlessness Osteoporosis

Wang

Ding

et al. 2022

Stem Cells International

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Objective. This study is aimed at screening the differential expression profiles of mRNA under weightlessness osteoporosis through high-throughput sequencing technology, as well as investigating the pathogenesis of weightlessness osteoporosis at the molecular level especially in bone marrow mesenchymal stem cells (BMSCs). Methods. The mouse bone marrow mesenchymal stem cell line was divided into ground group and simulated microgravity (SMG) group. BMP-2 was used to induce osteogenic differentiation, and SMG group was placed into 2D-gyroscope to simulate weightless condition. Transcriptome sequencing was performed by Illumina technology, DEGs between ground and SMG group was conducted using the DEseq2 algorithm. Molecular functions and signaling pathways enriched by DEGs were then comprehensively analyzed via multiple bioinformatic approaches including but not limited to GO, KEGG, GSEA, and PPI analysis. Results. A total of 263 DEGs were identified by comparing these 2 groups, including 186 upregulated genes and 77 downregulated genes. GO analysis showed that DEGs were enriched in osteoblasts, osteoclasts cell proliferation, differentiation, and apoptosis; KEGG analysis revealed that DEGs were significantly enriched in the TNF signaling pathway and FoxO signaling pathway; the enrichment results from Reactome database displayed that DEGs were mainly involved in the transcription of Hoxb3 gene, RUNX1 recruitment KMT2A gene, and activation of Hoxa2 chromatin signaling pathway. The four genes, IL6, CXCR4, IGF1, and PLOD2, were identified as hub genes for subsequent analysis. Conclusions. This study elucidated the significance of 10 hub genes in the development of weightlessness osteoporosis. In addition, the results of this study provide a theoretical basis and novel ideas for the subsequent research of the pathogenesis and clinical treatment of weightlessness osteoporosis.

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Transcriptome profiling reveals target in primary myelofibrosis together with structural biology study on novel natural inhibitors regarding JAK2

Cited by 9 publications

References 50 publications

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD

Revealing the Key MSCs Niches and Pathogenic Genes in Influencing CEP Homeostasis: A Conjoint Analysis of Single-Cell and WGCNA

High-Throughput Sequencing Reveals CXCR4 and IGF1 Behave Different Roles in Weightlessness Osteoporosis

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