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pmid:33381243
Identification of miRNAs as the Crosstalk in the Interaction between Neural Stem/Progenitor Cells and Endothelial Cells.
Xin Wang · Simin Li · Yihong Ma · Yuzhen Xu · Anthony Chukwunonso Ogbuehi · Xianda Hu · Aneesha Acharya · Rainer Haak · Dirk Ziebolz · Gerhard Schmalz · Hanluo Li · Sebastian Gaus · Bernd Lethaus · Vuk Savkovic · Zhiqiang Su
Disease markers · 2020 doi:10.1155/2020/6630659
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Complete file
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Differential expression analysis (DEA) was applied to identify NSPC-induced EC alterations by comparing the expression profiles between monoculture of ECs and ECs grown in EC/NSPC cocultures. DEA was also utilized to identify EC-induced NSPC alterations by comparing the expression profiles between monoculture of NSPCs and NSPCs grown in EC/NSPC cocultures. The DEGs and DEmiRNAs shared by NSPC-induced EC alterations and EC-induced NSPC alterations were then identified. Furthermore, miRNA crosstalk analysis and functional enrichment analysis were performed, and the relationship between DEmiRNAs and small molecular drug targets/environment chemical compounds was investigated.\nRESULTS: One dataset (GSE29759) was included and analyzed in this study. Six genes (i.e., MMP14, TIMP3, LOXL1, CCK, SMAD6, and HSPA2), three miRNAs (i.e., miR-210, miR-230a, and miR-23b), and three pathways (i.e., Akt, ERK1/2, and BMPs) were identified as crosstalk molecules. Six small molecular drugs (i.e., deptropine, fluphenazine, lycorine, quinostatin, resveratrol, and thiamazole) and seven environmental chemical compounds (i.e., folic acid, dexamethasone, choline, doxorubicin, thalidomide, bisphenol A, and titanium dioxide) were identified to be potential target drugs of the identified DEmiRNAs.\nCONCLUSION: To conclude, three miRNAs (i.e., miR-210, miR-230a, and miR-23b) were identified to be crosstalks linking the interaction between ECs and NSPCs by implicating in both angiogenesis and neurogenesis. These crosstalk molecules might provide a basis for devising novel strategies for fabricating neurovascular models in stem cell tissue engineering.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis was performed using the R package “limma” [13] for identifying differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) relevant to EC-induced NSPC changes and NSPC-induced EC changes, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33381243", "locator": "sections[4] \"2.2. 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NA means not overlapped between the EC-PPI and NSPC-PPI networks.", "structure": {"pmcid": "PMC7758130", "section_index": 16, "section_title": "3.4. EC-PPI Network and NSPC-PPI Network", "row_count": 31, "column_count": 8}, "table": {"label": "Table 5", "caption": "The topological characteristics of the top 30 nodes in the PPI network of EC-induced NSPC genetic alterations. NA means not overlapped between the EC-PPI and NSPC-PPI networks.", "rows": [["Gene", "Overlap", "Regulate", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["Gapdh", "NA", "Down", "129", "2.303797", "0.21952", "0.434066", "0.040603"], ["Fn1", "NA", "Down", "83", "2.586881", "0.062983", "0.386566", "0.054676"], ["Vegfa", "NA", "Down", "64", "2.638665", "0.041079", "0.37898", "0.063087"], ["Decr1", "NA", "Down", "59", "2.609896", "0.066189", "0.383157", "0.059219"], ["Cd44", "NA", "Down", "57", "2.693901", "0.029026", "0.371209", "0.069522"], ["Ccnd1", "NA", "Down", "54", "2.703107", "0.040282", "0.369945", "0.065015"], ["Gfap", "NA", "Down", "51", "2.663982", "0.042334", "0.375378", "0.070175"], ["Gad1", "NA", "Up", "47", "2.837745", "0.023163", "0.352393", "0.075753"], ["Cxcr4", "NA", "Down", "45", "2.805524", "0.015376", "0.35644", "0.091761"], ["Pkm", "NA", "Down", "45", "2.780207", "0.042856", "0.359685", "0.072881"], ["Anxa5", "NA", "Down", "41", "2.817031", "0.007322", "0.354984", "0.091351"], ["Timp1", "NA", "Down", "41", "2.805524", "0.010114", "0.35644", "0.09083"], ["Agt", "NA", "Down", "40", "2.857307", "0.014755", "0.34998", "0.0945"], ["Cav1", "NA", "Down", "40", "2.788262", "0.021742", "0.358646", "0.081866"], ["H6pd", "Overlap", "Down", "39", "2.905639", "0.018002", "0.344158", "0.081197"], ["Calb1", "NA", "Up", "39", "2.827388", "0.022978", "0.353683", "0.082931"], ["Ctgf", "NA", "Down", "38", "2.79977", "0.019484", "0.357172", "0.08851"], ["Pdgfrb", "NA", "Down", "38", "2.840046", "0.010704", "0.352107", "0.092062"], ["Snap25", "NA", "Up", "38", "2.840046", "0.026457", "0.352107", "0.071554"], ["Fos", "NA", "Down", "37", "2.757192", "0.026678", "0.362688", "0.086654"], ["Gad2", "NA", "Up", "37", "2.842348", "0.016537", "0.351822", "0.0868"], ["Anxa1", "NA", "Down", "36", "2.912543", "0.010209", "0.343343", "0.091158"], ["Tpi1", "NA", "Down", "36", "2.905639", "0.015808", "0.344158", "0.086608"], ["Gria1", "NA", "Up", "35", "2.837745", "0.033782", "0.352393", "0.079529"], ["Ldha", "NA", "Down", "35", "2.933257", "0.010636", "0.340918", "0.096276"], ["Thy1", "NA", "Down", "35", "2.886076", "0.018426", "0.346491", "0.090796"], ["Tubb3", "NA", "Up", "35", "2.829689", "0.013785", "0.353396", "0.087982"], ["Npy", "NA", "Up", "34", "2.906789", "0.010344", "0.344022", "0.099831"], ["Sst", "NA", "Up", "34", "2.921749", "0.012787", "0.342261", "0.101852"], ["Gng3", "NA", "Up", "32", "3.179517", "0.007673", "0.314513", "0.107118"]], "row_count": 31, "column_count": 8, "numeric_cells": 152, "header_rows": 1, "locator": "section[16]/table-wrap[2]#tab5"}}, {"id": "asset:table:pmid:33381243:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9c64330d8972dce0c6a20c7d930484b9e18c711247528a8f33846ca175acc27f", "bytes": 2612, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[3]#tab6", "version": null, "note": "The topological characteristics of overlapped DEGs in the PPI network of NSPC-induced EC genetic alterations. The overlapped DEGs mean these DEGs were overlapped between the PPI network of NSPC-induced EC alteration and the PPI network of EC-induced NSPC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 16, "section_title": "3.4. EC-PPI Network and NSPC-PPI Network", "row_count": 33, "column_count": 7}, "table": {"label": "Table 6", "caption": "The topological characteristics of overlapped DEGs in the PPI network of NSPC-induced EC genetic alterations. The overlapped DEGs mean these DEGs were overlapped between the PPI network of NSPC-induced EC alteration and the PPI network of EC-induced NSPC alteration.", "rows": [["Overlapped DEGs", "Regulate", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["Timp3", "Down", "21", "3.394397", "0.012355", "0.294603", "0.193591"], ["Mmp14", "Down", "15", "3.321121", "0.006668", "0.301103", "0.213333"], ["Col11a1", "Down", "14", "3.681034", "0.000966", "0.271663", "0.265873"], ["H3f3b", "Up", "13", "3.793103", "3.40E − 05", "0.263636", "0.329522"], ["Loxl1", "Down", "13", "3.568966", "0.001462", "0.280193", "0.254605"], ["Ccp110", "Up", "12", "3.497845", "0.007609", "0.28589", "0.324906"], ["Rpl30", "Up", "12", "3.715517", "0.001937", "0.269142", "0.208333"], ["Irs1", "Down", "11", "3.103448", "0.01987", "0.322222", "0.171937"], ["Aldh1a1", "Down", "9", "3.403017", "0.022894", "0.293857", "0.139918"], ["P4ha2", "Down", "9", "3.913793", "0.00226", "0.255507", "0.381313"], ["Cck", "Up", "8", "3.579741", "0.011327", "0.27935", "0.194444"], ["Plod2", "Down", "8", "4.118534", "7.55E − 06", "0.242805", "0.428977"], ["Rhoq", "Down", "8", "4.008621", "0.012817", "0.249462", "0.156863"], ["H6pd", "Down", "7", "3.534483", "0.017785", "0.282927", "0.159664"], ["Luc7l3", "Up", "7", "3.571121", "0.009536", "0.280024", "0.188065"], ["Dlx5", "Up", "6", "3.784483", "0.007836", "0.264237", "0.215278"], ["Rcn3", "Down", "6", "3.525862", "0.008417", "0.283619", "0.330247"], ["F3", "Down", "5", "3.56681", "7.31E − 06", "0.280363", "0.413514"], ["Hspa2", "Down", "5", "3.221983", "0.000827", "0.310368", "0.275229"], ["Tgm2", "Down", "5", "3.538793", "0.005005", "0.282582", "0.379221"], ["Aldh1a7", "Down", "4", "4.165948", "0.000317", "0.240041", "0.416667"], ["Irgm2", "Down", "4", "4.290948", "0.000557", "0.233049", "0.3125"], ["Smad6", "Down", "4", "3.928879", "0.002692", "0.254526", "0.289474"], ["Bmper", "Down", "3", "4.810345", "0.000753", "0.207885", "0.433333"], ["Daam2", "Down", "3", "3.87931", "0.008654", "0.257778", "0.333333"], ["Rras", "Down", "3", "4.3125", "0.000343", "0.231884", "0.439394"], ["Syde1", "Down", "3", "4.939655", "0.000344", "0.202443", "0.545455"], ["Tns1", "Down", "3", "4.286638", "0.002258", "0.233283", "0.355556"], ["Fcgrt", "Down", "2", "4.157328", "0", "0.240539", "0.576923"], ["Rin2", "Down", "2", "4.681034", "0.000218", "0.213628", "0.5"], ["Sdpr", "Down", "2", "4.275862", "0.000187", "0.233871", "0.5"], ["Slc2a10", "Down", "2", "4.176724", "0", "0.239422", "0.738095"]], "row_count": 33, "column_count": 7, "numeric_cells": 165, "header_rows": 1, "locator": "section[16]/table-wrap[3]#tab6"}}, {"id": "asset:table:pmid:33381243:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d7b0368b259d69a7b48d3dc166355b4d5f23d4fbf0255fe396992d61bc451e88", "bytes": 3362, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[4]#tab7", "version": null, "note": "The topological characteristics of overlapped DEGs in the PPI network of EC-induced NSPC genetic alterations. The overlapped DEGs mean these DEGs were overlapped between the PPI network of NSPC-induced EC alteration and the PPI network of EC-induced NSPC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 16, "section_title": "3.4. EC-PPI Network and NSPC-PPI Network", "row_count": 45, "column_count": 7}, "table": {"label": "Table 7", "caption": "The topological characteristics of overlapped DEGs in the PPI network of EC-induced NSPC genetic alterations. The overlapped DEGs mean these DEGs were overlapped between the PPI network of NSPC-induced EC alteration and the PPI network of EC-induced NSPC alteration.", "rows": [["Overlapped DEGs", "Regulate", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["H6pd", "Down", "39", "2.905639", "0.018002", "0.344158", "0.081197"], ["Mmp2", "Down", "30", "2.905639", "0.009375", "0.344158", "0.111791"], ["Cck", "Up", "24", "3.161105", "0.002392", "0.316345", "0.14388"], ["Irs1", "Down", "24", "2.90794", "0.011375", "0.343886", "0.090661"], ["Igfbp5", "Down", "18", "3.002302", "0.001391", "0.333078", "0.145524"], ["Loxl1", "Down", "18", "3.331415", "0.002588", "0.300173", "0.154147"], ["Mmp14", "Down", "18", "2.958573", "0.006212", "0.338001", "0.147655"], ["Aldh1a1", "Down", "16", "3.079402", "0.008487", "0.324738", "0.124419"], ["Plod2", "Down", "16", "3.535098", "0.002197", "0.282878", "0.168269"], ["Col11a1", "Down", "15", "3.464902", "0.007219", "0.288608", "0.154386"], ["Timp3", "Down", "15", "3.065593", "0.004764", "0.326201", "0.152648"], ["Irgm2", "Down", "14", "3.910242", "4.82E − 05", "0.255739", "0.348397"], ["P4ha2", "Down", "14", "3.637514", "0.001633", "0.274913", "0.177721"], ["Rhoq", "Down", "13", "3.673188", "0.001094", "0.272243", "0.173382"], ["F3", "Down", "11", "3.150748", "0.00066", "0.317385", "0.188776"], ["Dlx5", "Up", "10", "3.500575", "0.001701", "0.285667", "0.221359"], ["Hspa2", "Down", "10", "3.356732", "0.009675", "0.297909", "0.113084"], ["Luc7l3", "Up", "9", "3.771001", "0.004972", "0.265182", "0.17284"], ["Syde1", "Down", "9", "3.562716", "0.005367", "0.280685", "0.202822"], ["Tgm2", "Down", "9", "3.103567", "0.002864", "0.32221", "0.194714"], ["Rras", "Down", "8", "3.651323", "0.00461", "0.273873", "0.227113"], ["Sdpr", "Down", "8", "3.372842", "0.002511", "0.296486", "0.180118"], ["Aldh1a7", "Down", "7", "3.686997", "0.000587", "0.271223", "0.221254"], ["Ccp110", "Up", "7", "3.982739", "0.002565", "0.251084", "0.159664"], ["Cdc7", "Up", "7", "3.821634", "0.000152", "0.261668", "0.313589"], ["Rcn3", "Down", "7", "3.697353", "0.000432", "0.270464", "0.249433"], ["Tns1", "Down", "7", "3.397008", "0.005802", "0.294377", "0.188729"], ["Zcchc12", "Up", "6", "3.775604", "0.006142", "0.264858", "0.217391"], ["Akap12", "Down", "5", "3.422325", "0.002599", "0.292199", "0.261111"], ["Daam2", "Down", "5", "3.658228", "0.000694", "0.273356", "0.303226"], ["H3f3b", "Up", "5", "4.362486", "6.29E − 05", "0.229227", "0.5125"], ["Rpl30", "Up", "5", "4.084005", "0.000687", "0.244858", "0.3"], ["Sema3c", "Down", "5", "3.528193", "0.002593", "0.283431", "0.2075"], ["Smad6", "Down", "5", "3.510932", "0.001004", "0.284825", "0.284848"], ["Bmper", "Down", "4", "4.210587", "0.00075", "0.237497", "0.26"], ["Rin2", "Down", "4", "3.874568", "0.002452", "0.258093", "0.25"], ["Gem", "Down", "3", "3.882624", "0.002302", "0.257558", "0.42735"], ["Selenbp1", "Down", "3", "4.462601", "0.000293", "0.224085", "0.458333"], ["Fcgrt", "Down", "2", "3.943613", "3.45E − 05", "0.253575", "0.5"], ["Slc2a10", "Down", "2", "3.864212", "6.35E − 05", "0.258785", "0.5"], ["Sytl2", "Down", "2", "3.759494", "0.000207", "0.265993", "0.5"], ["Fam102a", "Down", "1", "5.730725", "0", "0.174498", "0"], ["Macrod1", "Down", "1", "5.880322", "0", "0.170059", "0"], ["Pdgfrl", "Down", "1", "4.286536", "0", "0.233289", "0"]], "row_count": 45, "column_count": 7, "numeric_cells": 228, "header_rows": 1, "locator": "section[16]/table-wrap[4]#tab7"}}, {"id": "asset:table:pmid:33381243:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fbfc25844e5903710568f6834f2706b3ef6e98c05d2f783096ec0e3ce063e308", "bytes": 2837, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#tab8", "version": null, "note": "The topological characteristics of the top 30 nodes in the TF-target DEG interaction network involved in the NSPC-induced EC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 17, "section_title": "3.5. The Transcription Factor-Target DEG Interaction Network", "row_count": 31, "column_count": 7}, "table": {"label": "Table 8", "caption": "The topological characteristics of the top 30 nodes in the TF-target DEG interaction network involved in the NSPC-induced EC alteration.", "rows": [["Name", "Label", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["Ptgs2", "Upregulated DEG", "30", "3.17073171", "0.25370241", "0.31538462", "0.07348485"], ["Il6", "Upregulated DEG", "20", "3.31300813", "0.16071429", "0.30184049", "0.10921053"], ["Serpine1", "Upregulated DEG", "19", "3.40650407", "0.10638454", "0.29355609", "0.09078947"], ["Mmp9", "Downregulated DEG", "18", "3.25203252", "0.16761464", "0.3075", "0.11243386"], ["Sp1", "TF", "15", "3.17479675", "0.15105709", "0.31498079", "0.10813008"], ["Nfkb1", "TF", "14", "2.99593496", "0.17606132", "0.33378562", "0.11316212"], ["Mmp2", "Downregulated DEG", "13", "3.45121951", "0.05861543", "0.28975265", "0.16008316"], ["Fgf10", "Downregulated DEG", "13", "4.18699187", "0.10945704", "0.23883495", "0.07692308"], ["Trp53", "TF", "13", "3.42276423", "0.10326907", "0.29216152", "0.10697115"], ["Jun", "TF", "13", "3.14634146", "0.14436348", "0.31782946", "0.12725546"], ["Twist1", "Downregulated DEG_TF", "12", "3.50406504", "0.13470851", "0.28538283", "0.13288288"], ["Col1a1", "Downregulated DEG", "12", "3.4796748", "0.11936909", "0.28738318", "0.13709677"], ["Birc5", "Upregulated DEG", "11", "3.53252033", "0.1098108", "0.283084", "0.13636364"], ["Csf2", "Upregulated DEG", "10", "3.51626016", "0.08268292", "0.28439306", "0.16071429"], ["Smad6", "Downregulated DEG", "9", "4.94715447", "0.04322026", "0.2021364", "0.12698413"], ["Stat3", "TF", "9", "3.43495935", "0.09055949", "0.29112426", "0.15065913"], ["Egr1", "TF", "9", "3.76829268", "0.05361397", "0.26537217", "0.13947991"], ["Nfe2l2", "Upregulated DEG_TF", "8", "3.89430894", "0.03472983", "0.25678497", "0.15972222"], ["Rela", "TF", "8", "3.33333333", "0.05841757", "0.3", "0.18382353"], ["Ep300", "TF", "8", "3.52439024", "0.04168611", "0.28373702", "0.19067797"], ["Upp1", "Upregulated DEG", "7", "3.58536585", "0.04680464", "0.27891156", "0.1978022"], ["Igf2", "Downregulated DEG", "7", "5.18292683", "0.04071495", "0.19294118", "0.14285714"], ["Ebf1", "Downregulated DEG_TF", "7", "4.57723577", "0.04361263", "0.21847247", "0.14285714"], ["Fos", "TF", "6", "3.82926829", "0.01974273", "0.2611465", "0.22727273"], ["Dcstamp", "Upregulated DEG", "6", "3.75203252", "0.02000123", "0.26652221", "0.25396825"], ["Nqo1", "Upregulated DEG", "5", "3.83333333", "0.02317522", "0.26086957", "0.21904762"], ["Ndrg1", "Downregulated DEG", "5", "3.83333333", "0.02104419", "0.26086957", "0.27142857"], ["Mmp14", "Downregulated DEG", "5", "3.81707317", "0.01378142", "0.26198083", "0.29"], ["Maf", "Downregulated DEG_TF", "5", "3.84146341", "0.0340471", "0.26031746", "0.28571429"], ["Hspa1b", "Downregulated DEG", "5", "3.88211382", "0.05662735", "0.25759162", "0.24545455"]], "row_count": 31, "column_count": 7, "numeric_cells": 154, "header_rows": 1, "locator": "section[17]/table-wrap[1]#tab8"}}, {"id": "asset:table:pmid:33381243:9", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:39d3a96de827ee8dc987622153032d252b34ff52c45b475dbaeade7eece8033c", "bytes": 2828, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#tab9", "version": null, "note": "The topological characteristics of the top 30 nodes in the TF-target DEG interaction network involved in the EC-induced NSPC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 17, "section_title": "3.5. The Transcription Factor-Target DEG Interaction Network", "row_count": 31, "column_count": 7}, "table": {"label": "Table 9", "caption": "The topological characteristics of the top 30 nodes in the TF-target DEG interaction network involved in the EC-induced NSPC alteration.", "rows": [["Name", "Label", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["Cdkn1a", "Downregulated DEG", "65", "2.73913043", "0.30858346", "0.36507937", "0.0283698"], ["Ccnd1", "Downregulated DEG_TF", "44", "2.90096618", "0.18721585", "0.34471274", "0.0390556"], ["Sp1", "TF", "38", "2.75120773", "0.18665254", "0.36347673", "0.04086687"], ["Fos", "Downregulated DEG_TF", "37", "2.89855072", "0.15489676", "0.345", "0.05012705"], ["Vegfa", "Downregulated DEG", "24", "3.09178744", "0.1032236", "0.3234375", "0.06904762"], ["Hes1", "Downregulated DEG_TF", "21", "3.26328502", "0.093159", "0.30643967", "0.06776557"], ["Cdkn2a", "Downregulated DEG", "20", "3.16183575", "0.06806015", "0.31627196", "0.0622093"], ["Nfkb1", "TF", "19", "2.83091787", "0.10896078", "0.35324232", "0.078356"], ["Cebpb", "Downregulated DEG_TF", "15", "3.01690821", "0.0630859", "0.33146517", "0.07979003"], ["Acta2", "Downregulated DEG", "14", "3.41062802", "0.04841393", "0.29320113", "0.10449735"], ["Trp53", "TF", "14", "3.23188406", "0.04815141", "0.30941704", "0.09895151"], ["Jun", "TF", "14", "3.25603865", "0.03607564", "0.30712166", "0.10204082"], ["Mmp2", "Downregulated DEG", "13", "3.08937198", "0.03126342", "0.32369038", "0.11609687"], ["Ep300", "TF", "12", "3.13043478", "0.05353532", "0.31944444", "0.11131841"], ["Cdkn2b", "Downregulated DEG", "12", "3.80917874", "0.03041314", "0.26252378", "0.10714286"], ["Nfe2l2", "Downregulated DEG_TF", "12", "3.26570048", "0.04141463", "0.30621302", "0.10585586"], ["Rela", "TF", "11", "3.21497585", "0.03799736", "0.31104433", "0.118411"], ["Nr3c1", "Downregulated DEG_TF", "11", "3.24637681", "0.03066868", "0.30803571", "0.11162255"], ["Smad6", "Downregulated DEG_TF", "11", "3.73671498", "0.02413405", "0.26761474", "0.11004785"], ["Sp3", "TF", "10", "3.35990338", "0.01668852", "0.29762761", "0.12268041"], ["Stat3", "TF", "10", "3.33816425", "0.03841092", "0.29956585", "0.13235294"], ["Id3", "Downregulated DEG", "10", "3.82125604", "0.02673839", "0.26169406", "0.10869565"], ["Smad3", "TF", "9", "3.72463768", "0.03330304", "0.26848249", "0.14403292"], ["Egr1", "TF", "9", "3.57004831", "0.03896833", "0.28010825", "0.12007168"], ["Mbp", "Downregulated DEG", "9", "3.52415459", "0.02687184", "0.283756", "0.13888889"], ["Srebf1", "TF", "8", "3.59903382", "0.0307691", "0.27785235", "0.13380282"], ["Myc", "TF", "8", "3.36231884", "0.02336862", "0.29741379", "0.14650538"], ["Id1", "Downregulated DEG_TF", "8", "3.2826087", "0.02185908", "0.30463576", "0.13903061"], ["Cebpd", "Downregulated DEG", "8", "3.43236715", "0.01679448", "0.29134412", "0.16163793"], ["Pdk4", "Downregulated DEG", "8", "3.61111111", "0.01282401", "0.27692308", "0.19396552"]], "row_count": 31, "column_count": 7, "numeric_cells": 152, "header_rows": 1, "locator": "section[17]/table-wrap[2]#tab9"}}, {"id": "asset:table:pmid:33381243:10", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:954ccb40064e73b3c675b77abf10e46b34123892cd0851b84125e06970e9ca27", "bytes": 1033, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tab10", "version": null, "note": "The number of experimentally validated, computationally predicted, and total miRNA-target DEG interaction pairs during the NSPC-induced EC alteration and EC-induced NSPC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 18, "section_title": "3.6. The DEmiRNAs-Target DEGs and Their Functions", "row_count": 3, "column_count": 5}, "table": {"label": "Table 10", "caption": "The number of experimentally validated, computationally predicted, and total miRNA-target DEG interaction pairs during the NSPC-induced EC alteration and EC-induced NSPC alteration.", "rows": [["Coculture-induced alterations in one type of cells", "Validated miRNA-target DEG pairs", "Predicted miRNA-target DEG pairs", "Total miRNA-target DEG pairs (including validated and predicted)", "Overlapped miRNA-target DEG interaction pairs (overlapped between NSPC-induced EC alteration and EC-induced NSPC alteration)"], ["NSPC-induced EC alteration", "536", "391", "810", "The overlapped 14 interaction pairs are as follows: miR-21-Rhoq, miR-23a-Akap12, miR-23a-Aldh1a1, miR-23a-Exoc3l4, miR-23a-Gm5424, miR-23a-Mfhas1, miR-23a-Nfe2l2, miR-23a-Slc16a6, miR-23b-Akap12, miR-23b-Aldh1a1, miR-23b-Gm5424, miR-23b-Mfhas1, miR-23b-Nfe2l2, and miR-23b-Slc16a6."], ["EC-induced NSPC alteration", "571", "243", "711"]], "row_count": 3, "column_count": 5, "numeric_cells": 7, "header_rows": 1, "locator": "section[18]/table-wrap[1]#tab10"}}, {"id": "asset:table:pmid:33381243:11", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0ec4dcea4e2dcbc6e5a81f6d720d9ba81fe01dfe03cfd4bbb0355d99f55db95b", "bytes": 2667, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[2]#tab11", "version": null, "note": "The topological characteristics of the top 30 nodes in the DEmiRNA-target network involved in the NSPC-induced EC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 18, "section_title": "3.6. The DEmiRNAs-Target DEGs and Their Functions", "row_count": 31, "column_count": 7}, "table": {"label": "Table 11", "caption": "The topological characteristics of the top 30 nodes in the DEmiRNA-target network involved in the NSPC-induced EC alteration.", "rows": [["Name", "lab2", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["mmu-miR-26a-2", "DEmiRNA", "2371", "2.195604", "0.216585", "0.455455", "0.221505"], ["mmu-miR-26a-1", "DEmiRNA", "2371", "2.195604", "0.216585", "0.455455", "0.221505"], ["mmu-let-7i", "DEmiRNA", "2244", "2.238546", "0.131513", "0.446719", "0.323641"], ["mmu-let-7c-2", "DEmiRNA", "2202", "2.252747", "0.110037", "0.443902", "0.332539"], ["mmu-let-7c-1", "DEmiRNA", "2202", "2.252747", "0.110037", "0.443902", "0.332539"], ["mmu-let-7a-2", "DEmiRNA", "1585", "2.461369", "0.051855", "0.406278", "0.376735"], ["mmu-let-7a-1", "DEmiRNA", "1585", "2.461369", "0.051855", "0.406278", "0.376735"], ["mmu-miR-23a", "DEmiRNA", "1297", "2.558749", "0.106936", "0.390816", "0.247494"], ["mmu-miR-23b", "DEmiRNA", "1269", "2.568216", "0.100185", "0.389375", "0.248916"], ["mmu-let-7d", "DEmiRNA", "1252", "2.573965", "0.063356", "0.388506", "0.353484"], ["mmu-miR-199a-2", "DEmiRNA", "839", "2.713609", "0.055721", "0.368513", "0.273838"], ["mmu-miR-199a-1", "DEmiRNA", "839", "2.713609", "0.055721", "0.368513", "0.273838"], ["mmu-miR-140", "DEmiRNA", "760", "2.740321", "0.114496", "0.364921", "0.175411"], ["mmu-miR-182", "DEmiRNA", "668", "2.771429", "0.088383", "0.360825", "0.194891"], ["mmu-miR-199b", "DEmiRNA", "660", "2.774134", "0.048537", "0.360473", "0.278883"], ["mmu-miR-210", "DEmiRNA", "468", "2.839053", "0.061318", "0.35223", "0.195913"], ["mmu-miR-99b", "DEmiRNA", "52", "2.979713", "0.006853", "0.335603", "0.234375"], ["Celf1", "Target gene", "16", "2.004227", "0.002733", "0.498946", "0.24026"], ["Taok1", "Target gene", "15", "2.179374", "0.001948", "0.458847", "0.263894"], ["Ubn2", "Target gene", "14", "2.137447", "0.001613", "0.467848", "0.279439"], ["Suco", "Target gene", "14", "2.137447", "0.001613", "0.467848", "0.279439"], ["Mtf2", "Target gene", "14", "2.186475", "0.001497", "0.457357", "0.28312"], ["Map3k2", "Target gene", "14", "2.162468", "0.001485", "0.462435", "0.282045"], ["Kdm6a", "Target gene", "14", "2.162468", "0.001485", "0.462435", "0.282045"], ["Ino80d", "Target gene", "14", "2.137109", "0.001824", "0.467922", "0.267984"], ["Celf2", "Target gene", "14", "2.090786", "0.001937", "0.478289", "0.265165"], ["Ankrd44", "Target gene", "14", "2.186475", "0.001497", "0.457357", "0.28312"], ["Tnpo1", "Target gene", "13", "2.196281", "0.001334", "0.455315", "0.291288"], ["Rfx7", "Target gene", "13", "2.144548", "0.001367", "0.466299", "0.28419"], ["Kmt2a", "Target gene", "13", "2.263567", "0.001442", "0.441781", "0.289898"]], "row_count": 31, "column_count": 7, "numeric_cells": 169, "header_rows": 1, "locator": "section[18]/table-wrap[2]#tab11"}}, {"id": "asset:table:pmid:33381243:12", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:90ca385bdcff709d28d8c0416748e266f9cbd05a6d9a6c7b401fa5e315417779", "bytes": 2610, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[3]#tab12", "version": null, "note": "The topological characteristics of the top 30 nodes in the DEmiRNA-target network involved in the EC-induced NSPC alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 18, "section_title": "3.6. The DEmiRNAs-Target DEGs and Their Functions", "row_count": 31, "column_count": 7}, "table": {"label": "Table 12", "caption": "The topological characteristics of the top 30 nodes in the DEmiRNA-target network involved in the EC-induced NSPC alteration.", "rows": [["Name", "lab2", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Topological coefficient"], ["mmu-let-7b", "DEmiRNA_up", "2362", "2.046362", "0.551173", "0.488672", "0.170618"], ["mmu-miR-124-1", "DEmiRNA_down", "1863", "2.247531", "0.154513", "0.444933", "0.394448"], ["mmu-miR-124-2", "DEmiRNA_down", "1863", "2.247531", "0.154513", "0.444933", "0.394448"], ["mmu-miR-124-3", "DEmiRNA_down", "1863", "2.247531", "0.154513", "0.444933", "0.394448"], ["mmu-miR-23a", "DEmiRNA_up", "1297", "2.475711", "0.158061", "0.403924", "0.306091"], ["mmu-miR-23b", "DEmiRNA_up", "1269", "2.486999", "0.14813", "0.402091", "0.309242"], ["mmu-miR-320", "DEmiRNA_up", "690", "2.720419", "0.141572", "0.36759", "0.217805"], ["mmu-miR-210", "DEmiRNA_up", "468", "2.809917", "0.093463", "0.355882", "0.206654"], ["Ino80d", "Target gene", "8", "1.998387", "0.0024", "0.500403", "0.294443"], ["Adam10", "Target gene", "8", "1.998387", "0.0024", "0.500403", "0.294443"], ["Mtf2", "Target gene", "8", "1.998387", "0.0024", "0.500403", "0.294443"], ["Pcdh19", "DEmRNA", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Rora", "DEmRNA", "7", "2.545051", "0.001403", "0.392919", "0.369491"], ["Ago2", "Target gene", "7", "2.1282", "0.00156", "0.469881", "0.338576"], ["Ago3", "Target gene", "7", "2.1282", "0.00156", "0.469881", "0.338576"], ["Col4a1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Cpd", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Map3k1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Mecp2", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Etnk1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Kpna1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Yod1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Prtg", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Slc36a1", "Target gene", "7", "2.1282", "0.00156", "0.469881", "0.338576"], ["Tet2", "Target gene", "7", "2.1282", "0.00156", "0.469881", "0.338576"], ["Ahctf1", "Target gene", "7", "2.1282", "0.00156", "0.469881", "0.338576"], ["Qser1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Wnk1", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Slc7a2", "Target gene", "7", "2.085467", "0.001524", "0.479509", "0.337695"], ["Aldh1l2", "Target gene", "7", "2.545051", "0.001403", "0.392919", "0.369491"]], "row_count": 31, "column_count": 7, "numeric_cells": 162, "header_rows": 1, "locator": "section[18]/table-wrap[3]#tab12"}}, {"id": "asset:table:pmid:33381243:13", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:caf7d3a08c2735dabfbb2c80167b7226539cb479736af8a5a7647cee9b2176c1", "bytes": 954, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#tab13", "version": null, "note": "The 16 small molecular drugs that were overlapped between NSPC-induced EC genetic alteration and EC-induced NSPC genetic alteration.", "structure": {"pmcid": "PMC7758130", "section_index": 19, "section_title": "3.7. Identifying Significant Small Molecular Drugs", "row_count": 17, "column_count": 3}, "table": {"label": "Table 13", "caption": "The 16 small molecular drugs that were overlapped between NSPC-induced EC genetic alteration and EC-induced NSPC genetic alteration.", "rows": [["Small molecular drugs", "Enrichment in the NSPC-induced EC alteration", "Enrichment in the EC-induced NSPC alteration"], ["2-Aminobenzenesulfonamide", "0.629", "-0.682"], ["Adiphenine", "0.748", "-0.693"], ["Deptropine", "-0.677", "-0.672"], ["Diphenhydramine", "0.67", "-0.573"], ["Felbinac", "0.719", "-0.697"], ["Fludrocortisone", "0.503", "-0.496"], ["Fluphenazine", "-0.357", "-0.378"], ["Ikarugamycin", "0.811", "-0.838"], ["Lycorine", "0.633", "0.776"], ["Milrinone", "-0.779", "0.73"], ["PHA-00745360", "0.567", "-0.514"], ["Podophyllotoxin", "0.661", "-0.933"], ["Quinostatin", "-0.992", "-0.954"], ["Resveratrol", "-0.479", "-0.504"], ["Thiamazole", "0.726", "0.543"], ["Triflupromazine", "0.694", "-0.71"]], "row_count": 17, "column_count": 3, "numeric_cells": 34, "header_rows": 1, "locator": "section[19]/table-wrap[1]#tab13"}}, {"id": "asset:table:pmid:33381243:14", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6eee76bae85ec6afb9b6ba0332997ba3af2cf3c3fd69748908d4a9950ec2c9f2", "bytes": 5039, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[1]#tab14", "version": null, "note": "The scores of the crosstalk miRNA interaction pairs under five conditions including the target genes, small molecular drugs, chemical compounds, signaling pathways, and biological processes. These crosstalk miRNAs link the EC-induced NSPC alteration process and NSPC-induced EC alteration process. The scores were calculated by the “Meet/Min” formula.", "structure": {"pmcid": "PMC7758130", "section_index": 21, "section_title": "3.9. Crosstalk miRNAs Linking the EC-Induced NSPC Alteration Process and NSPC-Induced EC Alteration Process", "row_count": 55, "column_count": 7}, "table": {"label": "Table 14", "caption": "The scores of the crosstalk miRNA interaction pairs under five conditions including the target genes, small molecular drugs, chemical compounds, signaling pathways, and biological processes. These crosstalk miRNAs link the EC-induced NSPC alteration process and NSPC-induced EC alteration process. The scores were calculated by the “Meet/Min” formula.", "rows": [["miRNAs involved in the NSPC-induced EC alteration", "miRNAs involved in the EC-induced NSPC alteration", "Score_target", "Score_molecular", "Score_chemical", "Score_pathway", "Score_bp"], ["mmu-miR-210", "mmu-miR-210", "1", "0.166667", "1", "1", "1"], ["mmu-miR-23b", "mmu-miR-23b", "1", "0.075", "1", "1", "1"], ["mmu-miR-23b", "mmu-miR-23a", "0.966903", "0.022222", "1", "0.946667", "0.931284"], ["mmu-miR-23a", "mmu-miR-23b", "0.966903", "0.05", "0.95", "0.946667", "0.931284"], ["mmu-let-7d", "mmu-let-7b", "0.834665", "0.021739", "0.2", "1", "0.862256"], ["mmu-miR-26a-1", "mmu-miR-23a", "0.393215", "0.05", "0.321429", "0.936709", "0.614696"], ["mmu-miR-26a-2", "mmu-miR-23a", "0.393215", "0.05", "0.321429", "0.936709", "0.614696"], ["mmu-miR-26a-1", "mmu-miR-23b", "0.389283", "0.025", "0.307692", "0.946667", "0.615335"], ["mmu-miR-26a-2", "mmu-miR-23b", "0.389283", "0.025", "0.307692", "0.946667", "0.615335"], 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"row_count": 55, "column_count": 7, "numeric_cells": 378, "header_rows": 1, "locator": "section[21]/table-wrap[1]#tab14"}}], "gaps": ["asset:data:geo:GSE29759 not downloaded", "asset:data:geo:GSE29759 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differential expression analysis was performed using the R package “limma” [13] for identifying differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) relevant to EC-induced NSPC changes and NSPC-induced EC changes, respectively."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE29759"], "resolved_accessions": ["GSE29759"], "statements": ["The data used to support the findings of this study are available from the corresponding author upon request."], "basis": "The paper names GSE29759 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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