KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
| Antibodies | ||
| HA (WB) | Biolegend | Cat# 901501 ; RRID: AB_2565006 |
| H3K27M (WB and immunohistochemistry) | EMD | Cat# ABE419 ; RRID: AB_2728728 |
| H3K27me3 (WB) | EMD | Cat# 07–449 ; RRID: AB_310624 |
| H3K27ac (WB) | abcam | Cat# ab177178 ; RRID: AB_2828007 |
| H3K4me1 (WB) | Cell signaling | Cat# 5326s ; RRID: AB_10695148 |
| H3K4me3 (WB) | Cell signaling | Cat# 9751s ; RRID: AB_2616028 |
| H3K36me3 (WB) | ACTIVE MOTIF | Cat# 61021 ; RRID: AB_2614986 |
| Total H3 (WB) | Cell signaling | Cat# 3638S ; RRID: AB_1642229 |
| H3K27me3 (ChIP-seq) | ACTIVE MOTIF | Cat# 39155 ; RRID: AB_2561020 |
| H3K27ac (ChIP-seq) | ACTIVE MOTIF | Cat# 39133 ; RRID: AB_2561016 |
| H3K4me1 (ChIP-seq) | ACTIVE MOTIF | Cat# 39297 ; RRID: AB_2615075 |
| H3K4me3 (ChIP-seq) | ACTIVE MOTIF | Cat# 39159 ; RRID: AB_2615077 |
| H3K27ac (immunohistochemistry) | Cell signaling | Cat# 8173 ; RRID: AB_10949503 |
| H3K27M (immunohistochemistry) | EMD | Cat# ABE419 ; RRID: AB_2728728 |
| H3K27me3 (immunohistochemistry) | EMD | Cat# 07–449 ; RRID: AB_310624 |
| SLC1A5 (immunohistochemistry) | Sigma | Cat# HPA035240 ; RRID: AB_10604092 |
| SLC2A3/GLUT3 (WB) | abcam | Cat# ab191071 ; RRID: AB_2736916 |
| HK2 (WB) | Santa Cruz bio | Cat# sc-374091;RRID:AB_10917915 |
| IDH1 (WB) | Cell signaling | Cat# 8137 ; RRID: AB_10950504 |
| IDH2 (WB) | Santa Cruz bio | Cat# sc-374476; RRID: AB_10986415 |
| GDH (GLUD1/2) (WB) | abcam | Cat# ab166618 ; RRID: |
| SLC7A11 (WB) | Cell signaling | Cat# 12691s ; RRID: AB_2687474 |
| β-ACTIN (WB) | Sigma | Cat# A5441 ; RRID: AB_476744 |
| GAPDH (WB) | Santa Cruz bio | Cat# sc-25778; RRID: AB_10167668 |
| p-s6rp (Ser240/244) (WB) | Cell signaling | Cat# 2215s ; RRID: AB_331682 |
| p-s6rp (Ser235/236) (WB) | Cell signaling | Cat# 4858s ; RRID: AB_916156 |
| s6rp (WB) | Cell signaling | Cat# 2317s ; RRID: AB_2238583 |
| N-myc (WB) | Santa Cruz bio | Cat# sc-53993; RRID: AB_831602 |
| C-myc (WB) | Santa Cruz bio | Cat# sc-40 ; RRID: AB_627268 |
| SLC1A5/ASCT2 (WB) | ThermoFisher | Cat# PA5–50527;RRID: AB_2635980 |
| GLS (WB) | abcam | Cat# ab156876 ; RRID: AB_2721038 |
| GSK3 a/b (WB) | Cell signaling | Cat# 5676s ; RRID: AB_10547140 |
| p-GSK3 a/b (Ser21/9) (WB) | Cell signaling | Cat# 9331s ; RRID: AB_329830 |
| VINCULIN (WB) | Sigma | Cat# V9264 ; RRID: AB_10603627 |
| FLAG (WB) | Cell signaling | Cat# 2368s ; RRID: AB_2217020 |
| GOT1 (WB) | Abcam | Cat# ab171939 |
| Hif-1α (WB) for mouse | Abcam | Cat# ab16066; RRID:AB_302234 |
| HIF-1α (WB) for human | Abcam | Cat# ab179483; RRID:AB_2732807 |
| Bacterial and Virus Strains | ||
| One-shot Stbl3 chemically competent E.coli | ThermoFisher | Cat# C737303 |
| Chemicals, Peptides, and Recombinant Proteins | ||
| DM-succinate | Acros Organics | Cat# AC150731000 |
| DM-αKG | Sigma | Cat# 349631 |
| DMSO | Sigma | Cat# D2650 |
| Glucose | Gibco | Cat# A2494001 |
| L-Glutamine | Gibco | Cat# 25030–081 |
| Matrix-gel (Matrigel® Basement Membrane Matrix) | Corning | Cat# 356234 |
| D-Luciferin, Potassium Salt | GoldBio | Cat# LUCK-1G |
| GSK-J4 | Cayman Chem. | Cat# 12073 |
| GSK-J5 | Cayman Chem. | Cat# 12074 |
| DON (6-Diazo-5-oxo-L-norleucine) | Cayman Chem. | Cat# 17580 |
| 2-DG (2-Deoxy-D-glucose) | Cayman Chem. | Cat# 14325 |
| D-2HG ((2R)-Octyl-α-hydroxyglutarate) | Cayman Chem. | Cat# 16366 |
| CB-839 | Cayman Chem. | Cat# 22038 |
| BPTES | Cayman Chem. | Cat# 19284 |
| Lonidamine | Cayman Chem. | Cat# 14640 |
| Ketoconazole | Cayman Chem. | Cat# 15212 |
| Posaconazole | Cayman Chem. | Cat# 14737 |
| Desferrioxamine | Cayman Chem. | Cat# 14595 |
| JHU-083 | MCE | Cat# HY-122218 |
| IDH1 inhibitor 1 | Abbvie | |
| IDH1 inhibitor 2 | Abbvie | |
| IDH1 inhibitor 3 | Abbvie | |
| IDH1 inhibitor 13 | Abbvie | |
| Inactive enone analogue 18 | Abbvie | |
| Critical Commercial Assays | ||
| TransIT®-Lenti Transfection Reagent | Mirus | Cat# MIR 6650 |
| TMT10plex™ Isobaric Label Reagent Set | ThermoFisher | Cat# 90110 |
| D-2-Hydroxyglutarate Assay Kit | abcam | Cat# ab211070 |
| Succinate Assay Kit (Colorimetric) | abcam | Cat# ab204718 |
| Alpha Ketoglutarate (alpha KG) Assay Kit | abcam | Cat# ab83431 |
| Deposited Data | ||
| NCBI/ GEO (GSE135419), next generation sequencing files. | This paper | GEO: GSE135419 |
| Experimental Models: Cell Lines | ||
| HSJD-DIPG007 (H3.3K27M) | Dr. Rintaro Hashizume, Northwestern University; RRID: CVCL_VU70 | |
| SU-DIPG-XIII (H3.3K27M) | Dr. Michelle Monje, Stanford University; RRID: CVCL_IT41 | |
| SU-DIPG-IV (H3.1K27M) | Dr. Michelle Monje, Stanford University; RRID: CVCL_IT39 | |
| SF7761 (H3.3K27M) | Dr. Rintaro Hashizume, Northwestern University; RRID: CVCL_IT45 | |
| SJGBM2 (H3WT) | Dr. Carl Koschmann, University of Michigan; RRID: CVCL_M141 | |
| SF188 (H3WT) | Dr. Craig B. Thompson, Memorial Sloan Kettering Cancer Center; RRID: CVCL_6948 | |
| UMPed37 (H3WT) | Dr. Carl Koschmann, University of Michigan | |
| KNS42 (H3.3G34V) | Dr. Carl Koschmann, University of Michigan; RRID: CVCL_0378 | |
| TB-096 (IDH1 R132H) | Dr. Hai Yan, Duke University | |
| mNSC | Dr. Richard J. Gilbertson, St Jude’s Hospital | |
| Experimental Models: Organisms/Strains | ||
| Mouse: Hsd:Athymic Nude-Foxn1nu | Jackson Laboratories | Cat# 002019; RRID: IMSR_JAX:002019 |
| Mouse: NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ | Jackson Laboratories | Cat#:005557; RRID: IMSR_JAX:005557 |
| Oligonucleotides | ||
| siRNA IDH1 NT: ON-TARGETplus Non-targeting Control siRNAs | Dharmacon | Cat# D-001810–01-05 |
| siRNA IDH1–1: ON-TARGETplus IDH1 siRNA Targeted Region:3'UTR | Dharmacon | Cat# J-008294–09-0002 |
| siRNA IDH1–2: ON-TARGETplus IDH1 siRNA Targeted Region:ORF | Dharmacon | Cat# J-008294–10-0002 |
| siRNA IDH1–3: ON-TARGETplus IDH1 siRNA Targeted Region:ORF | Dharmacon | Cat# J-008294–11-0002 |
| Recombinant DNA | ||
| H3.3WT lentiviral plasmid | Dr. David Allis, The Rockefeller University | |
| H3.3K27M lentiviral plasmid | Dr. David Allis, The Rockefeller University | |
| shNT lentiviral plasmid | Sigma | Cat# SHC002V |
| shGLUD1–1 lentiviral plasmid | Sigma | Cat# TRCN0000343656 |
| shGLUD1–2 lentiviral plasmid | Sigma | Cat# TRCN0000028600 |
| shHK2–1 lentiviral plasmid | Sigma | Cat# TRCN0000037670 |
| shHK2–2 lentiviral plasmid | Sigma | Cat# TRCN0000195582 |
| shIDH1 lentiviral plasmid (V2LHS_217815) | Dharmacon | Cat# RHS4430–200189861 |
| pLenti PGK Blast V5-LUC | Addgene | Cat# 19166 ; RRID: Addgene_19166 |
| pSLIK-IDH1-FLAG | Addgene | Cat# 66802 ; RRID: Addgene_66802 |
| pSLIK-IDH1-R132H-FLAG | Addgene | Cat# 66803 ; RRID: Addgene_66803 |
| Software and Algorithms | ||
| PRISM 7.0/8.0 | GraphPad | |
| Image Studio software | LI-COR | |
| IVIS Living Image Software | Perkin Elmer | |
| IGV(Integrative Genomics Viewer) 2.5.0 | Broad Institute | |
| AperioImageScope/ AperioScan Scope | Aperio | |
| RSEM (RNA-Seq by Expectation-Maximization) | https://deweylab.github.io/RSEM/ | |
| CASAVA 1.8.2 pipeline | Illumina | |
| methylKit | https://bioconductor.org/packages/release/bioc/html/methylKit.html | |
| Proteome Discoverer v2.1 | Thermo Fisher | |
| SICER | http://www.lcmodel.com/ | |
| MACS | http://liulab.dfci.harvard.edu/MACS/ | |
| Agilent MassHunter Workstation Software Quantitative | Agilent | |
| GSEA | Broad Institute http://software.broadinstitute.org/gsea/index.jsp |
|
| MetaboAnalyst | https://www.metaboanalyst.ca/ | |
| Matlab’s image processing toolbox | Matlab | |
| Image Studio software | Licor | |