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Sidoli"],"technology_type":["Mass Spectrometry","Bottom-up proteomics"],"software":[""],"submitter_keywords":["Ngfr","Chromatin","Carm1","Glioblastoma","Akt","Arginine methylation","Glioma stem-like cell","Nfia","Proteomics","Histones","Development","Entrectinib","Ntrk","Radial glial cell","Erk"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD080227"],"tissue":["Brain"],"sample_protocol":["Proteomic analysis  After desalting, samples were resuspended in 0.1% Formic Acid (FA) and loaded onto the Bruker nanoElute 2 coupled online with the timsTOF HT (Bruker). Chromatography separation was used using a two-column system consisting of a C18 trap cartridge (ThermoFisher #174500) and an analytical PepSep XTREME column of 25cm x 150µm x 1.5µm (Bruker #1893476). Samples were separated using a 45 minute gradient from 4 to 30% buffer B at a flow rate of 700nl (Buffer A: 0.1% FA, Buffer B: 80% acetonitrile + 0.1% FA). The spectra were acquired in dia-PASEF in the range of 100-1700 m/z and 0.6 1/K0 [V-s/cm-2] to 1.6 1/K0 [V-s/cm-2]. Ramp and accumulation times were set to 100. 32 DIA isolation windows were used in the range of 400-1201 m/z and 0.6 1/K0 [V-s/cm-2] to 1.6 1/K0 [V-s/cm-2]. The collision energy was ramped as a function of increasing mobility starting from 20 eV at 0.60 1/K0 to 59 eV at 1.6 1/K0.   Post desalting, samples were resuspended in 0.1% TFA and placed onto the Dionex RSLC Ultimate 300 and analyzed by an Orbitrap Fusion Lumos (ThermoFisher). A two column system was used to separate the histone peptides composed of a C18 trap cartridge (300 µm ID, 5 mm length) and an analytical column (75 µm, 25 cm). The analytical column was packed in our lab with reversed-phase Repro-Sil Pur C18-AQ 3 µm resin. Histone peptides were separated using a 30 minute gradient and at a flow rate of 300nl/min in DIA mode. The full MS scan was set to 300-1100 m/z in the orbitrap with a resolution of 120,000 (at 200m/z)."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Proteomic analysis  The MS raw data was searched using FragPipe version 22 [29] with the preloaded workflow “DIA_ SpecLib_Quant_diaPASEF”. Our digestive enzymes were trypsin or chymotrypsin (for CARM1 substrate analysis only). Using R, raw protein abundances were log2 transformed, normalized by median centering, and imputed using a normal distribution two standard deviations beneath the mean as described previously [30]. For CARM1 ADMA substrate and phospho-proteomics analysis we added another normalization step in which normalized ADMA peptides and phospho-peptides were divided by the normalized total protein abundance of their respective proteins. This approach allows us to quantify the differential abundance of the specific PTMs while removing any bias that may be introduced due to differences in total protein abundance. For statistical analysis, equality of variances between groups was first assessed using an F-test, followed by either Welch's t-test for unequal variances or Student's t-test for equal variances with alpha level of 0.05 for statistically significant results. Proteins/peptides were considered differentially expressed only if they were statistically significant in both sgCARM1-1 and sgCARM1-2.  Histone post-translational modification (PTMs) analysis Raw data files were searched through EpiProfile 2.0 software [31], and the area under the curve was generated for each identified histone peptide. To properly normalize the data, the sum of every identified combination for a histone peptide was summed (total peptide abundance) and considered to be 100% and the area of each individual peptide was divided by the total peptide abundance to generate a ratio. The relative ratio of two isobaric forms was calculated by averaging the ratio for each fragment ion between the two. Using R, the final peptide table was log2 transformed, log2foldchange was calculated, and statistical testing was performed by first assessing equality of variances between groups using an F-test, followed by either Welch's t-test for unequal variances or Student's t-test for equal variances with alpha level of 0.05 for statistically significant results. All histone PTMs were only considered differentially expressed if they were statistically significant in both sgCARM1-1 and sgCARM1-2."],"omics_type":["Proteomics"],"labhead":["Simone Sidoli"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States"],"species":["Homo Sapiens (human)"],"publication":["Not available"],"submitter_mail":["simone.sidoli@gmail.com"],"submitter_affiliation":["Albert Einstein College of Medicine"],"submitter_country":["United States"],"additional_accession":[]},"is_claimable":false,"name":"Depletion of CARM1 slows in-vivo tumorigenicity and rewires developmental programming in Glioma stem-like cells","description":"Glioma stem-like cells (GSCs) exploit developmental signaling programs that contribute to glioblastoma heterogeneity and therapy resistance. Here, we define a role for the arginine methyltransferase CARM1 in regulating GSC lineage state and survival signaling. CARM1 depletion slows GSC growth, increases apoptosis, alters histone post-translational modifications, and shifts transcriptomic and proteomic profiles toward a radial glial-like state. Loss of CARM1 increases NGFR/NTRK signaling and sensitizes GSCs to NTRK and AKT inhibition. Mechanistically, NFIA is a CARM1 substrate, and mutation of NFIA arginine 389 increases NGFR expression, supporting a role for CARM1-dependent NFIA methylation in NGFR repression. In orthotopic xenografts, CARM1 depletion reduces tumor burden and prolongs survival. These findings identify CARM1 as a regulator of GSC developmental programs and NGFR/NTRK-dependent survival.","dates":{"publication":"2026-06-28","submission":"2026-06-26"},"accession":"PXD080227","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:1584","NEWT:36630","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:55350","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:1912919","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2709072","NEWT:2499525","NEWT:2853422","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:237610","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:1640278","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:906914","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:42410","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:49012","NEWT:6493","NEWT:10832","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:595495","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:1613","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:353153","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:13037","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:475932","NEWT:256318","NEWT:20641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