KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Phospho-Cyclin B1 (S133) | Cell Signaling | Cat. #4133; RRID:AB_2072264 |
| Cyclin B1 | ThermoFisher | Cat. #MA5-14319; RRID:AB_10987286 |
| cTnT-647 | BD Biosciences | Cat. #565744; RRID:AB_2739341 |
| cTnT | ThermoFisher | Cat. #MA5-12960; RRID:AB_11000742 |
| TnI | Santa Cruz | Cat. #sc-15368; RRID:AB_793465 |
| Alpha-actinin | Sigma | Cat. #A7811; RRID:AB_476766 |
| Alpha-actinin | Abcam | Cat. #AB9465; RRID:AB_307264 |
| p53 (ChIP-validated) | Cell Signaling | Cat. #48818; RRID:AB_2713958 |
| p21 | Cell Signaling | Cat. #2947; RRID:AB_823586 |
| GAPDH | Cell Signaling | Cat. #5174; RRID:AB_10622025 |
| Phospho-H2AX (S139) | Cell Signaling | Cat. #9718; RRID:AB_2118009 |
| Phospho-AMPK (Thr172) | Cell Signaling | Cat. #2535; RRID:AB_331250 |
| AMPK | Cell Signaling | Cat. #5832; RRID:AB_10624867 |
| GFP-488 | BioLegend | Cat. #338008; RRID:AB_2563288 |
| Phospho-Histone H3 (Ser28) 647 | BioLegend | Cat. #641005; RRID:AB_1279419 |
| Ki67-PE-Cy7 | BD | Cat. #561283; RRID:AB_10716060 |
| Aurora Kinase A | Cell Signaling | Cat. #14475; RRID:AB_2665504 |
| b-MHC | DSHB | Cat. #A4.951; RRID:AB_528385 |
| Peroxidase-conjugated anti-BrdU | Roche | Cat. #11585860001; RRID:AB_514485 |
| Ki67-647 | BD | Cat. #558615; RRID:AB_647130 |
| Goat anti-mouse PE | Jackson | Cat. #115-116-072; RRID:AB_2338627 |
| Goat anti-mouse 488 | Invitrogen | Cat. #A11001; RRID:AB_2534069 |
| Goat anti-mouse 594 | Invitrogen | Cat. #A11005; RRID:AB_2534073 |
| Goat anti-rabbit 594 | Invitrogen | Cat. #A11012; RRID:AB_2534079 |
| Rabbit anti-mouse 488 | Invitrogen | Cat. #A11059; RRID:AB_2534106 |
| Biotin-SP goat anti-mouse | Jackson ImmunoResearch | Cat. #115-065-003; RRID:AB_2338557 |
| Goat anti-rabbit IgG HRP | Cell Signaling | Cat. #7074; RRID:AB_2099233 |
| Goat anti-mouse IgG HRP | Invitrogen | Cat. #A11008; RRID:AB_143165 |
| H3K27ac (ChIP-validated) | Diagenode | Cat. #C15410196; RRID:AB_2637079 |
| H3K4me1 (ChIP-validated) | Diagenode | Cat. #C15410194; RRID:AB_2637078 |
| H3K4me2 (ChIP-validated) | Abcam | Cat. #AB7766; RRID:AB_2560996 |
| H3K4me3 (ChIP-validated) | Diagenode | Cat. #C15410003; RRID:AB_2616052 |
| H3K27me3 (ChIP-validated) | Diagenode | Cat. #C15410195; RRID:AB_2753161 |
| H3K9me3 (ChIP-validated) | Diagenode | Cat. #C15410193; RRID:AB_2616044 |
| H3K36me3 (ChIP-validated) | Diagenode | Cat. #C15410192; RRID:AB_2744515 |
| IgG control (ChIP-validated) | Cell Signaling | Cat. #2729; RRID:AB_1031062 |
| Critical commercial assays | ||
| NextSeq 500/550 v2 | Illumina | Cat. #FC4042005 |
| Absurance H3 Histone Peptide Array | Millipore | Cat. #16667 |
| SMARTer ThruPLEX DNA-seq | Takara | Cat. #R400427 |
| NEBNext Library Quant kit | New England BioLabs | Cat. #E7630 |
| Nextera XT Library Prep kit | Illumina | Cat. #15032354 |
| HiFi DNA Assembly | New England BioLabs | Cat. #E2621 |
| Seahorse XF Cell Mito Stress | Agilent | Cat. #103015-100 |
| Ex-Taq polymerase | Takara | Cat. #RR001C) |
| Qubit dsDNA kit | Invitrogen | Cat. #Q32854 |
| iDeal ChIP Kit for Transcription Factors | Diagenode | Cat. #C01010055 |
| Fast SYBR Green Master Mix | Applied Biosystems | Cat. #4385612 |
| HT 8-oxo-dG ELISA kit | Trevigen | Cat. #4380-096-K |
| Click-iT Plus EdU Alexa Fluor 647 Flow Cytometry Assay Kit |
Invitrogen | Cat. #C10635 |
| AF647 tyramide | ThermoFisher | Cat. #B40916 |
| Click-iT Plus TUNEL Alexa Fluor 594 Assay Kit |
Invitrogen | Cat. #C10618 |
| Experimental models: Cell lines and animals | ||
| PGP1 human iPSCs | Coriell | Cat. #GM23338 |
| PC1 human iPSCs | Christine Seidman, Harvard | (Hinson et al., 2016) |
| WTC-11 human iPSCs | Gladstone, UCSF | A gift from Dr. Bruce Conklin |
| Sprague-Dawley rats | Harlan/Envigo | N/A |
| HEK293T | ATCC | Cat. #CRL3216 |
| Oligonucleotides | ||
| Brunello sgRNA library | Addgene | Cat. #73178 |
| HR220PA | SBI | Cat. #HR220PA-1 |
| EditR-Cas9 | Dharmacon | Cat. #CAS10138 |
| psPAX2 | Addgene | Cat. #12260 |
| pCMV-VSV-G | Addgene | Cat. #8454 |
| LentiGuide-Puro | Addgene | Cat. #52963 |
| pCas9-GFP | Addgene | Cat. #44719 |
| pLenti CMV GFP Puro | Addgene | Cat. #17448 |
| PX459v2 | Addgene | Cat. #62988 |
| Oliognucleotides for custom sgRNA library | IDT | Custom order |
| Oligonucleotides for scRNA-seq UMIs | IDT | Custom order |
| Software and algorithms | ||
| MAGeCK | Bitbucket | https://bitbucket.org/liulab/mageck/src/master/ |
| DiffBind | Bioconductor | https://bioconductor.org/packages/DiffBind |
| rGREAT | Bioconductor | https://bioconductor.org/packages/rGREAT |
| Homerkit | GitHub | https://github.com/slowkow/homerkit |
| Rtsne | GitHub | https://github.com/jkrijthe/Rtsne |
| Seurat | GitHub | https://github.com/satijalab/seurat |
| STAR (v.2.5.4a) | GitHub | https://github.com/alexdobin/STAR |
| Molecular Signature Database | Broad | https://www.gsea-msigdb.org/gsea/msigdb/index.jsp |
| EdgeR | Bioconductor | https://bioconductor.org/packages/release/bioc/html/edgeR.html |
| CellView | GitHub | https://github.com/mohanbolisetty/CellView |
| GraphPad Prism | GraphPad Software | http://survey-smiles.com |
| FlowJo | FLOWJO | https://flowjo.com |
| Fiji | NIH | https://fiji.sc |
| Drop-seq_tools | GitHub | https://github.com/broadinstitute/Drop-seq/releases/tag/v1.13 |
| Calcium signal analysis | (Pettinato et al., 2020) | https://github.com/TheJacksonLaboratory/hinson_excel_signal2 |
| Chemicals, peptides, and recombinant proteins | ||
| IWP4 | Tocris | Cat. #5214 |
| CHIR99021 | Tocris | Cat. #4423 |
| Y-276932 | Tocris | Cat. #1254 |
| Nutlin-3 | Sigma | Cat. #444151 |
| Fibronectin (human) | Corning | Cat. #33016015 |
| Matrigel GFR | Corning | Cat. #354230 |
| Insulin (human) | Sigma | Cat. #91077C |
| Verapamil | Tocris | Cat. #0654 |
| NAC | Alfa Aesar | Cat. #A1540914 |
| GeneJuice Transfection Reagent | EMD Millipore | Cat. #709675 |
| GoTaq Flexi DNA polymerase | Promega | Cat. #M8297 |
| ROCK inhibitor Y-27632 | Tocris | Cat. #1254 |
| CHIR99021 | Cayman | Cat. #13122 |
| Wnt-C59 | Selleck | Cat. #S7037 |
| Fibronectin | Fisher | Cat. #33-016-015 |
| Benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoro-methyl ketone (ZVAD) | Millipore | Cat. #627610 |
| Bcl-XL BH4 | Millipore | Cat. #197217 |
| Cyclosporine A | Novartis | |
| IGF-1 | Peprotech | Cat. #100-11 |
| Pinacidil | Sigma | Cat. #P154 |
| 5-Bromo-2’-deoxyuridine (BrdU) | Sigma | Cat. #B5002 |
| Other | ||
| Accutase | BD Biosciences | Cat. #561527 |
| RPMI 1640 | ThermoFisher | Cat. #11875093 |
| DMEM (glucose-free) | GIBCO | Cat. #11966025 |
| Opti-MEM | GIBCO | Cat. #31985062 |
| Polyethylenimine (PEI) | Polysciences | Cat. #239662 |
| PEG-6000 | Millipore Sigma | Cat. #528877 |
| Trypsin-EDTA | GIBCO | Cat. #25200056 |
| Geneticin (G418) | GIBCO | Cat. #10131035 |
| Zeocin | GIBCO | Cat. #R25005 |
| Protein G Dynabeads | ThermoFisher | Cat. #10004 |
| Puromycin | GIBCO | Cat. #A1113803 |
| Blasticidin | GIBCO | Cat. #A1113903 |
| B27 supplement | GIBCO | Cat. #17504044 |
| B27 supplement (−insulin) | GIBCO | Cat. #A1895601 |
| Penicillin/Streptomycin | GIBCO | Cat. #15140122 |
| GlutaMAX | GIBCO | Cat. #35050061 |
| Sodium lactate | Sigma | Cat. #71718 |
| N-acetylcysteine (NAC) | MilliporeSigma | Cat. #1064255 |
| mTeSR1 | STEMCELL Technologies | Cat. #85850 |
| DAPI | Invitrogen | Cat. #D1306 |
| TO-PRO-3 | Invitrogen | Cat. #T3605 |
| Hoechst 33342 | ThermoFisher | Cat. #62249 |
| MitoTracker Green | Invitrogen | Cat. #M7514 |
| MitoSOX Red | Invitrogen | Cat. #M36008 |
| Fetal bovine serum (heat-inactivated) | Gemini | Cat. #100-106 |
| Protein G Dynabeads | ThermoFisher | Cat. #10014 |
| PBS | GIBCO | Cat. #10010049 |
| picoGreen | ThermoFisher | Cat. #P7589 |
| KOD Hot Start Master Mix | MilliporeSigma | Cat. #71842-4 |
| SuperSignal West Pico Chemiluminescent substrate | ThermoFisher | Cat. #34580 |
| ProLong Gold Mountant | Invitrogen | Cat. #P36965 |
| 4–20% Mini-PROTEAN TGX gels | Bio-Rad | Cat. #4561095 |
| RTA PVDF Transfer kit | Bio-Rad | Cat. #1704272 |
| BSA, Fraction V | Fisher | Cat. #BP1605 |
| Pyruvate | GIBCO | Cat. #11360070 |
| Tris-Glycine SDS 10X | Fisher | Cat. #BP13414 |
| Maxima H Minus Reverse Transcriptase | ThermoFisher | Cat. #EP0751 |
| Exo I | New England BioLabs | Cat. #M0293 |
| AMPure beads | Beckman Coulter | Cat. #A63881 |
| KAPA HiFi | Kapa Biosystems | Cat. #KM2602 |
| DH5a E.coli cells | New England BioLabs | Cat. #C2987 |
| Stbl3 E.coli cells | Invitrogen | Cat. #C737303 |
| Stbl4 E.coli cells | Invitrogen | Cat. #11635018 |
| 4mm cuvettes | Bio-Rad | Cat. #1652088 |
| RIPA buffer | Cell Signaling | Cat. #9806 |
| Protease inhibitor cocktail | Roche | Cat. #11836170001 |
| Phosphatase inhibitor | Pierce | Cat. #A32957 |
| BCA kit | ThermoFisher | Cat. #23225 |
| Protein sample buffer | ThermoFisher | Cat. #39000 |
| Puromycin | ThermoFisher | Cat. #A1113803 |
| Versene | ThermoFisher | Cat. #15040066 |
| PBS | GIBCO | Cat. #14190144 |
| RPMI | GIBCO | Cat. #11875093 |
| Bovine Serum Albumin | Sigma | Cat. #A9418 |
| Ascorbic Acid | Sigma | Cat. #A8960 |
| FBS | BioWest | Cat. #S1620 |
| 0.05% Trypsin-EDTA | GIBCO | Cat. #25300054 |
| Saponin | Sigma | Cat. #47036 |
| CryoStor | Sigma | Cat. #C2874 |
| Diaminobenzadene (DAB) | Vector Labs | Cat. #PK-6100 |
| Deposited data | ||
| scRNA-seq data | GEO | GEO: GSE147249 |
| CRISPR screen data | GEO | GEO: GSE147417 |
| ChIP-seq data | GEO | GEO: GSE130285 |