KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Cytochrome C – AF 647 | BioLegend | Cat# 612310, RRID:AB_2565241 |
| CD45 – APC | BD | Cat# 559864 RRID:AB_398672 |
| GAPDH (0411) HRP | Santa Cruz | Cat# sc-47724 HRP RRID:AB_627678 |
| HRI (D-12) | Santa Cruz | Cat# sc-365239 RRID:AB_10843794 |
| eIF2alpha | CST | Cat# 9722 RRID:AB_2230924 |
| eIF2 pS51 | Abcam | Cat# ab32157 RRID:AB_732117 |
| ATF-4 | CST | Cat# 11815 RRID:AB_2616025 |
| HRI (D-12) (EIF2AK1) | Proteintech | Cat# 20499-1-AP RRID:AB_10697665 |
| PKR (EIF2AK2) | Santa Cruz | Cat# sc6282 RRID:AB_628150 |
| Perk (EIF2AK3) | CST | Cat# 3192 RRID:AB_2095847 |
| GCN2 (EIF2AK4) | CST | Cat# 40457 RRID:AB_2799177 |
| Nrf2 | Santa Cruz | Cat# sc13032 RRID:AB_2263168 |
| Heme Oxygenase 1 Antibody (A-3) | Santa Cruz | Cat# sc-136960 RRID:AB_2011613 |
| GAPDH-HRP | Santa Cruz | Cat# sc47724-HRP RRID:AB_627678 |
| β-Actin Antibody (C4) HRP | Santa Cruz | Cat# sc-47778 HRP RRID:AB_2714189 |
| Caspase9 | CST | Cat# 9502S RRID:AB_2068621 |
| HCCS | Abcam | Cat# ab234874 |
| APAF-1 | CST | Cat# 5088S RRID:AB_10556958 |
| BAX | CST | Cat# 2772 RRID:AB_10695870 |
| BAK | CST | Cat# 3814 RRID:AB_2290287 |
| BOK | Abcam | Cat# ab186745 RRID:AB_2728737 |
| Cytochrome c (D18C7) Rabbit mAb | CST | Cat# 11940S RRID:AB_2637071 |
| Amersham ECL Rabbit IgG, HRP-linked whole Ab (from donkey) | Amersham | Cat# NA934 RRID:AB_772206 |
| Cytiva’s Amersham ECL Mouse IgG, HRP-linked whole Ab (from sheep) | Amersham | Cat# NA931 RRID:AB_772210 |
| Anti-NRF2 antibody [N2C2] | Genetex | Cat# GTX103322 RRID:AB_1950993 |
| GFP-Booster Alexa Fluor® 488 | Chromotek | Cat# gb2AF488 RRID:AB_2827573 |
| RFP-Booster Alexa Fluor® 568 | Chromotek | Cat# rb2AF568 RRID:AB_2827576 |
| BODIPY™ 581/591 C11 | Thermo Fisher | Cat# D3861 |
| Cytochrome C | BD | Cat# 556432 RRID:AB_396416 |
| GFP-Trap Magnetic Agarose | Chromotek | Cat# gtma-20 RRID:AB_2631358 |
| p62/SQSTM1 | Sigma | Cat# P0067 RRID:AB_1841064 |
| Bacterial and Virus Strains | ||
| NEB®10-beta Competent E.coli (High Efficiency) | NEB | Cat# C3019H |
| NEB 5-alpha Competent E.coli | NEB | Cat# C2987H |
| NEB® Stable Competent E.coli (High Efficiency) | NEB | Cat# C3040H |
| TOPO™ TA Cloning™ Kit for Sequencing, with One Shot™ TOP10 Chemically Competent E. coli | Thermo Fisher | Cat# K4575J10 |
| Biological Samples | ||
| - | ||
| Chemicals, Peptides, a Recombinant Proteins | ||
| ABT-737 | MCE | Cat# HY-50907 |
| S63845 | MCE | Cat# HY-100741 |
| ISRIB | MCE | Cat# HY-12495 |
| 2BAct | AOBIOUS | Cat# 2143542-28-1 |
| Paclitaxel | MCE | Cat# HY-B0015 |
| RSL3 | Selleck Chemicals | Cat# S8155 |
| Irinotecan | MCE | Cat# HY-16562 |
| Erlotinib | Cayman | Cat# 10483 |
| Vemurafenib (PLX4032) | Cayman | Cat# 10618 |
| Raptinal | Millipore Sigma | Cat# SML1745 |
| Digitonin | Sigma-Aldrich | Cat# D141 |
| Eif2s1, His tagged human,recombinant | Sigma-Aldrich | Cat# SRP5232 |
| Eif2ak1 (HRI) Human Protein | Thermo Scientific | Cat# PV5856 |
| 3X FLAG® Peptide | Sigma-Aldrich | Cat# F4799 |
| AC DEVD AFC | Enzo Life Sciences | Cat# ALX260032M005 |
| Cytochrome c from Saccharomyces cerevisiae | Sigma-Aldrich | Cat# C2436 |
| Cytochrome C, equine | Sigma-Aldrich | Cat# C2506 |
| Cytochrome C, bovine | Sigma-Aldrich | Cat# C2037 |
| Liberase TM | Sigma-Aldrich | Cat# 5401119001 |
| DNase I, Grade II, from bovine pancreas | Sigma-Aldrich | Cat# 10104159001 |
| Corning® Matrigel® Basement Membrane Matrix, LDEV-Free | Corning | Cat# 356234 |
| Deferoxamine mesylate salt | Sigma-Aldrich | Cat# D9533-1G |
| Critical Commercial Assays | ||
| RNeasy Mini Kit | Qiagen | Cat#74104 |
| Direct-zol RNA MicroPrep (200 Preps) w/ Zymo-Spin IC Columns (Capped) | Zymo Research | Cat# R2062 |
| Intracellular Fixation & Permeabilization Buffer Set | BD | Cat# 554714 |
| eBioscience Foxp3 / Transcription Factor Staining Buffer Set | Thermo Scientific | Cat# 00-5523-00 |
| Dual-Luciferase Reporter 1000 Assay System | Promega | Cat# E1980 |
| CellTiter-Glo Luminescent Cell Viability Assay | Promega | Cat# G7572 |
| CellTrace™ CFSE Cell Proliferation Kit, for flow cytometry | Thermo Scientific | Cat# C34554 |
| Cell Trace Violet | Thermo Scientific | Cat# C34557 |
| Clarity™ Western ECL Substrate, 500 ml, 1705061 | Bio-Rad | Cat# 1705061 |
| Xt MES Running Buffer, 1610789 | Bio-Rad | Cat# 1610789 |
| 20S Proteasome Lysis Buffer | CAYMAN Chemicals | Cat# 10011098 |
| Lipofectamine 3000 Transfection Reagen | Thermo Scientific | Cat# L3000001 |
| Fugene HD Transfection Reagent, Promega, FuGENE HD Transfection | Promega | Cat# E2311 |
| ViaFect Transfection Reagent | Promega | Cat# E4981 |
| Lipofectamine™ RNAiMAX Transfection Reagent | Therno Scientific | Cat# 13778075 |
| Ercc RNA Spike-In Mix | Thermo Scientific | Cat# 4456740 |
| pcDNA3.1/V5-His TOPO TA Expression Kit | Thermo Scientific | Cat# K480001 |
| ANTI-FLAG® M2 Affinity Gel,purified immunoglobulin, buffered aqueous | Sigma-Aldrich | Cat# A2220 |
| SYBR Green PCR Master Mix | Applied Biosystems | Cat#4309155 |
| Chromium Next GEM Single Cell 3ʹ Library Kit v3.1 16 rxns | 10X Genomics | PN-1000157 |
| Chromium Next GEM Chip G Single Cell Kit, 16 rxns | 10X Genomics | PN-100012 |
| Mycoalert Detection kit | Lonza | Cat# LT07-318 |
| EasySep Dead Cell Removal (Annexin V) kit | STEMCELL technologies | Cat# 17899 |
| Next Seq 500/550 High Output Kit v2 | Illumina | Cat#FC-404-2002 |
| TruSeq Stranded mRNA kits | Illumina | Cat#20020595 |
| Zombie Violet Viability Kit | Biolegend | Cat#423113 |
| Deposited Data | ||
| SuperSeries | GSE189639 | |
| bulk RNA-seq of parental and persister cells generated human cancer cells | GSE189625 | |
| scRNAseq of PC9 parental and persister cells | GSE189638 | |
| Experimental Models: Cell Lines | ||
| H. sapiens: PC9 | ATCC | |
| H. sapiens: HCT116 | Richard Youle | |
| H. sapiens: HT29 | ATCC | |
| H. sapiens: A549 | Richard J. Webby, SJRH | |
| H. sapiens: H226 | ATCC | |
| Experimental Models: Organisms/Strains | ||
| NOD.Cg-Prkdcsscid Il2rgtm1Wjl/SzJ (NSG) | In house | |
| Rag1−/− | In house | |
| Oligonucleotides | ||
| sgRNA see Table S3 | abm (Lopez et al., 2016; Shalem et al., 2014) | N/A |
| siRNA see Table S4 | Dharmacon, IDT | N/A |
| qPCR primer see Table S5 | Origene sequences, (Kim et al., 2010; Spandidos et al., 2008, 2010; Wang et al., 2012) | N/A |
| Recombinant DNA | ||
| Piggybac expression system (inducible) | (Magnúsdóttir et al., 2013) | |
| pPB constitutive CMV | This paper | |
| pPB (puro)-mCherry | This paper | |
| pPB (puro)-mNeonGreen | This paper | |
| pPB (puro)_hUTR(ATF4) luci_IRES RenLuciferase | This paper | |
| pPB (puro) mitoV1 AifTail-mCh-GFP1-10 | This paper | |
| pPB (Blast) | This paper | |
| pPB (Blast) 2xGFP11 (M3) | This paper | |
| pPB (Zeo) | This paper | |
| pPB (Zeo)_CYCS | This paper | |
| pPB (Zeo)_CYCS K72R | This paper | |
| pPB Luciferase-tdTomato | This paper | |
| pcDNA TOPO TA mClover | This paper | |
| pXG290 (HRI-mClover) | (Guo et al., 2020) | Addgene 141284 |
| Px458 pSpCas9(BB)-2A-GFP | (Ran et al., 2013) | Addgene 48138 |
| pLKO5.sgRNA.EFS.PAC | (Heckl et al., 2014) | Addgene 57825 |
| CRISPRv2 GFP | (Walter et al., 2017) | Addgene 82416 |
| pSpCas9(BB)-2A-mCherry | In House | N/A |
| Software and Algorithms | ||
| Trim Galore (v0.5.0) | Babraham Institute | RRID:SCR_011847 |
| Picard (v 2.19.0) | Broad Institute | RRID:SCR_006525 |
| RSEM | Dewey lab | RRID:SCR_013027 |
| DESeq2 (v1.30.1) | Michael Love | RRID:SCR_015687 |
| Cell Ranger (v6.0.1) | 10X Genomics | RRID:SCR_017344 |
| Slingshot (v1.8.0) | Kelly Street | RRID:SCR_017012 |
| STAR (v 2.7.5a) | Alexander Dobin | RRID:SCR_004463 |
| Seurat (v4.0.4) | Satija lab | RRID:SCR_016341 |
| tradeSeq (v1.4.0) | Lieven Clement | RRID:SCR_019238 |
| clusterProfiler (v3.18.1) | Guangchuang Yu | RRID:SCR_016884 |
| R (v 4.0.5) | R project | RRID:SCR_001905 |
| RUVseq (v1.24.0) | Davide Risso | RRID:SCR_006263 |
| FlowJo v10 | FlowJo, LLC | RRID:SCR_008520 |
| Slidebook 6 | Intelligent Imaging Innovations | RRID:SCR_014300 |
| GraphPad Prism 9.0 | GraphPad Software | RRID:SCR_002798 |
| IMARIS 9.8 | Oxford Instruments | RRID:SCR_007370 |