REAGENT or RESOURCE | SOURCE | IDENTIFIER |
---|---|---|
Antibodies | ||
Rabbit monoclonal anti-phospho-TBK1/NAK (Ser172) (D52C2) antibody | Cell Signaling Technology | Cat# 5483; RRID: AB_10693472 |
Rabbit monoclonal anti-TBK1/NAK (D1B4) antibody | Cell Signaling Technology | Cat# 3504; RRID: AB_2255663 |
Rabbit monoclonal anti-phospho-IRF-3 (Ser396) (D6O1M) antibody | Cell Signaling Technology | Cat# 29047; RRID: AB_2773013 |
Rabbit polyclonal anti-IRF-3 (FL-425) antibody | Santa Cruz Biotechnology | Cat# sc-9082; RRID: AB_2264929 |
Rabbit monoclonal anti-phospho-NF-κB p65 (Ser536) (93H1) antibody | Cell Signaling Technology | Cat# 3033; RRID: AB_331284 |
Rabbit monoclonal anti-NF-κB p65 (C22B4) antibody | Cell Signaling Technology | Cat# 4764; RRID: AB_823578 |
Rabbit monoclonal anti-TFAM (D5C8) antibody | Cell Signaling Technology | Cat# 8076; RRID: AB_10949110 |
Rabbit monoclonal anti-STING (D2P2F) antibody | Cell Signaling Technology | Cat# 13647; RRID: AB_2732796 |
Rabbit monoclonal anti-cleaved Caspase-3 (Asp175) (5A1E) antibody | Cell Signaling Technology | Cat# 9664; RRID: AB_2070042 |
Rabbit polyclonal anti-GFP antibody | Thermo Fisher Scientific | Cat# A-11122; RRID: AB_221569 |
Rabbit polyclonal anti-TDP-43 antibody | Thermo Fisher Scientific | Cat# PA5-27221; RRID: AB_2544697 |
Rabbit polyclonal anti-AGK antibody | Atlas Antibodies | Cat# HPA020959; RRID: AB_1854206 |
Rabbit monoclonal anti-Cyclophilin F [EPR11311-121] antibody | Abcam | Cat# ab231155 |
Rabbit polyclonal anti-MAVS (Rodent specific) antibody | Cell Signaling Technology | Cat# 4983; RRID: AB_823566 |
Rabbit monoclonal anti-Histone H3 (D1H2) antibody | Cell Signaling Technology | Cat# 4499; RRID: AB_10544537 |
Rabbit monoclonal anti-GAPDH (14C10) antibody | Cell Signaling Technology | Cat# 2118; RRID: AB_561053 |
Mouse monoclonal anti-ATP5A antibody [15H4C4] | Abcam | Cat# ab14748 |
Mouse monoclonal anti-PKR (B-10) antibody | Santa Cruz Biotechnology | Cat# sc-6282; RRID: AB_628150 |
Mouse monoclonal anti-cGAS (D-9) antibody | Santa Cruz Biotechnology | Cat# sc-515777; RRID: AB_2734736 |
Rat monoclonal anti-FLAG (9H1) antibody | In-House | N/A |
Mouse monoclonal anti-β-Actin (C4) antibody | Santa Cruz Biotechnology | Cat# sc-47778 HRP; RRID: AB_2714189 |
Mouse monoclonal anti-DNA (AC-30-10) antibody | Progen | Cat# 61014; RRID: AB_2750935 |
Rabbit monoclonal anti-TOMM20 [EPR15581-54] Alexa Fluor 647 antibody | Abcam | Cat# ab209606 |
Rabbit polyclonal anti-TIMM44 antibody | Sigma-Aldrich | Cat# HPA043052; RRID: AB_10795713 |
Goat anti-Rat IgG H&L Alexa Fluor 405 antibody | Abcam | Cat# ab175671 |
Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody Alexa Fluor 488 antibody | Thermo Fisher Scientific | Cat# A-11001; RRID: AB_25344069 |
Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody Alexa Fluor 568 antibody | Thermo Fisher Scientific | Cat# A-11011; RRID: AB_143157 |
Rabbit polyclonal anti-MNX1 (HB9) antibody | Millipore | Cat# ABN174; RRID: AB_27322012 |
Goat polyclonal anti-Choline Acetyltransferase antibody | Millipore | Cat# AB144P; RRID: AB_2079751 |
Mouse monoclonal anti-βIII Tubulin (5G8) antibody | Promega | Cat# G7121; RRID: AB_430874 |
Rat monoclonal anti-Myc tag [9E10] antibody | Abcam | Cat# ab206486 |
Anti-FLAG M2 Affinity Gel antibody | Sigma Aldrich | Cat# A2220; RRID: AB_10063035 |
Biological Samples | ||
Human post-mortem spinal cord tissues (sALS and MS) | Victorian Brain Bank | Table S1 |
Chemicals, Peptides, and Recombinant Proteins | ||
FuGENE HD Transfection Reagent | Promega | Cat# E2311 |
Lipofectamine 2000 Transfection Reagent | Thermo Fisher Scientific | Cat# 11668030 |
Ethidium bromide | Sigma-Aldrich | Cat# E8751; CAS 1239-45-8 |
Uridine | Sigma-Aldrich | Cat# U3003; CAS 58-96-8 |
Geneticin Selective Antibiotic (G418 Sulfate) | Thermo Fisher Scientific | Cat# 11811023; CAS 108321-42-2 |
Doxycycline hyclate | Sigma-Aldrich | Cat# D9891; CAS 24390-14-5 |
Blasticidin | InvivoGen | Cat# ant-bl-1 |
Poly(dA:dT) | InvivoGen | Cat# tlrl-patn; CAS 86828-69-5 |
Deoxyribonucleic acid sodium salt from herring testes (HT-DNA) | Sigma-Aldrich | Cat# D6898; CAS 438545-06-3 |
2′3′-c-di-AM(PS)2(Rp, Rp) | InvivoGen | Cat# tlrl-nacda2r; CAS 1638750-95-4 |
ABT-737 | Active Biochemicals | Cat# A-1002; CAS 852808-04-9 |
MitoSOX™ Red | Thermo Fisher Scientific | Cat# M36008 |
Tetramethylrhodamine methyl ester perchlorate (TMRM) | Thermo Fisher Scientific | Cat# T5428; CAS 115532-50-8 |
Cyclosporin A | Sigma-Aldrich | Cat# C3662; CAS 59865-13-3 |
RU.521 (cGAS inhibitor) | M. Ascano Laboratory | Vincent et al., 2017 |
H-151 (STING inhibitor) | Life Chemicals | Haag et al., 2018 |
Mitoquinol | Cayman Chemical | Cat# 89950; CAS 845959-55-9 |
MitoTEMPO (hydrate) | Cayman Chemical | Cat# 16621; CAS 1569257-94-8 |
TDP-43 inhibitor peptide PM1 (YGRKKRRQRRRAQFPGACGL) | This paper | Wang et al., 2016 |
TDP-43 control peptide CM1 (YGRKKRRQRRRAAQGFGCPL) | This paper | Wang et al., 2016 |
Primocin | InvivoGen | Cat# ant-pm-1 |
Y-27632 (RHO/ROCK pathway inhibitor) | STEMCELL Technologies | Cat# 72304; CAS 129830-38-2 |
CHIR99021 (GSK3 inhibitor) | STEMCELL Technologies | Cat# 72054; CAS 252917-06-9 |
Dorsomorphin (BMP and AMPK inhibitor) | STEMCELL Technologies | Cat# 72102; CAS 866405-64-3 |
SB431542 Hydrate (Activin/BMP/TGF-b pathway inhibitor) | STEMCELL Technologies | Cat# 72234; CAS 301836-41-9 |
All trans-Retinal | Sigma-Aldrich | Cat# R2500; CAS 116-31-4 |
Purmorphamine (Hedgehog pathway activator) | STEMCELL Technologies | Cat# 72202; CAS 483367-10-8 |
L-Ascorbic acid | Sigma-Aldrich | Cat# A4403; CAS 50-81-7 |
Valproic Acid (Sodium Salt) | STEMCELL Technologies | Cat# 72292; CAS 1069-66-5 |
Compound E | STEMCELL Technologies | Cat# 73954; CAS 209986-17-4 |
Paraformaldehyde 16% aqueous solution | ProSciTech | Cat# C004; CAS 30525-89-4 |
Glutaraldehyde solution | Sigma-Aldrich | Cat# 340855; CAS 111-30-8 |
VBIT-4 (VDAC1 oligomerization inhibitor) | MedChemExpress | Cat# HY-129122; CAS 2086257-77-2 |
Digitonin | Sigma-Aldrich | Cat# D141; CAS 11024-24-1 |
cOmplete Protease Inhibitor Cocktail | Roche Biochemicals | Cat# 11836145001 |
IGF1 recombinant human protein | Thermo Fisher Scientific | Cat# PHG0078 |
RPMI-1640 | In-House | N/A |
Dulbecco’s Modified Eagle Medium (DMEM) | Thermo Fisher Scientific | Cat# 11965092 |
DME/KELSO Medium | In-House | N/A |
Hank’s Balanced Salt Solution (HBSS) | Thermo Fisher Scientific | Cat# 14170112 |
Matrigel hESC-Qualified Matrix | Corning | Cat# 354277 |
mTeSR™1 | STEMCELL Technologies | Cat# 85850 |
ReLeSR | STEMCELL Technologies | Cat# 05872 |
KnockOut DMEM/F-12 | Thermo Fisher Scientific | Cat# 12660012 |
Neurobasal Medium | Thermo Fisher Scientific | Cat# 21103049 |
N-2 Supplement (100X) | Thermo Fisher Scientific | Cat# 17502048 |
B-27 Supplement (50X) | Thermo Fisher Scientific | Cat# 17504044 |
Accutase cell detachment solution | STEMCELL Technologies | Cat# 07920 |
TrypLE Express Enzyme | Thermo Fisher Scientific | Cat# 12604013 |
Normal Goat Serum (10%) | Thermo Fisher Scientific | Cat# 50062Z |
Critical Commercial Assays | ||
QuikChange Lightning Mutagenesis Kit | Agilent Technologies | Cat# 210513 |
Lactate Dehydrogenase Activity Assay Kit | Sigma-Aldrich | Cat# MAK066 |
VeriKine-HS Mouse Interferon Beta Serum ELISA Kit | PBL Assay Science | Cat# 42410-1 |
VeriKine-HS Human Interferon Beta Serum ELISA Kit | PBL Assay Science | Cat# 41415-1 |
Human CXCL10/IP-10 Quantikine ELISA kit | R&D Sysytems | Cat# SIP100 |
2′3′-cGAMP ELISA Kit | Cayman Chemical | Cat# 501700 |
Deposited Data | ||
Original blots | This paper | Mendeley Data: https://doi:10.17632/kx9v83c65r.1 |
Experimental Models: Cell Lines | ||
Human embryonic kidney (HEK) 293T | ATCC | CRL-3216 |
AGKFlp-In control HEK293T | Diana Stojanovski Laboratory | Kang et al., 2017 |
AGK−/− HEK293T | Diana Stojanovski Laboratory | Kang et al., 2017 |
AGK−/− +WT HEK293T | Diana Stojanovski Laboratory | Kang et al., 2017 |
AGK−/− +G126E-3XFLAG HEK293T | Diana Stojanovski Laboratory | Kang et al., 2017 |
THP-1 human monocytic cells (sex: male, age: 1) | ATCC | TIB-202 |
THP-1 Cas9-mCherry cells | This paper | N/A |
THP-1 pSLIK-neo cells | This paper | N/A |
THP-1 pSLIK-TDP-43 WT cells | This paper | N/A |
THP-1 pSLIK-TDP-43 Q331K cells | This paper | N/A |
THP-1 STINGCRISPR−/− cells | This paper | N/A |
THP-1 STINGCRISPR−/− pSLIK-neo cells | This paper | N/A |
THP-1 STINGCRISPR−/− pSLIK-TDP-43 WT cells | This paper | N/A |
THP-1 STINGCRISPR−/− pSLIK-TDP-43 Q331K cells | This paper | N/A |
WT Immortalized mouse embryonic fibroblasts (MEFs) (sex: ND) | This paper | N/A |
MAVS−/− MEFs (sex: ND) | Sandra Nicholson Laboratory | Nguyen et al., 2017 |
cGAS−/− MEFs (sex: ND) | Benjamin Kile Laboratory | White et al., 2014 |
STING−/− MEFs (sex: ND) | Benjamin Kile Laboratory | White et al., 2014 |
Bak−/−/Bax−/− MEFs (sex: ND) | Benjamin Kile Laboratory | White et al., 2014 |
Vdac1−/−/Bak−/− MEFs (sex: ND) | Grant Dewson Laboratory | Chin et al., 2018 |
Vdac1−/−/Bax−/− MEFs (sex: ND) | Grant Dewson Laboratory | Chin et al., 2018 |
PKR−/− MEFs (sex: ND) | Anthony Sadler Laboratory | Irving et al., 2012 |
Mcl1−/− Cas9/Blasticidin MEFs | This paper | N/A |
Mcl1−/− pSLIK-neo MEFs | This paper | N/A |
Mcl1−/− pSLIK-hTDP-43 WT MEFs | This paper | N/A |
Mcl1−/− pSLIK-hTDP-43 Q331K MEFs | This paper | N/A |
PpidCRISPR−/− pSLIK-neo MEFs | This paper | N/A |
PpidCRISPR−/− pSLIK-hTDP-43 WT MEFs | This paper | N/A |
PpidCRISPR−/− pSLIK-hTDP-43 Q331K MEFs | This paper | N/A |
Mouse motor neuron-like hybrid cells NSC-34 (sex: ND) | Cellutions Biosystems | CLU140 |
pSLIK-neo NSC-34 | This paper | N/A |
pSLIK-hTDP-43 WT NSC-34 | This paper | N/A |
pSLIK-hTDP-43 Q331K NSC-34 | This paper | N/A |
Human iPSC healthy control HC1 (NCRM-1) (male, cord blood) | National Institute of Neurological Disorders and Stroke | Efthymiou et al., 2015 |
Human iPSC healthy control HC2 (NCRM-5) (male, cord blood) | National Institute of Neurological Disorders and Stroke | Efthymiou et al., 2015 |
Human iPSC healthy control HC3 (WT1) (sex: ND, age: 8) | Alessandro Rosa Laboratory | Lenzi et al., 2015 |
Human iPSC healthy control HC4 (female, age: 62) | This paper | N/A |
Human iPSC healthy control HC5 (male, age: 74) | This paper | N/A |
Human iPSC healthy control HC6 (female, age: 88) | This paper | N/A |
Human iPSC ALS-TARDBP G298S (TALSTDP-47.10) (male, age: 43) | Target ALS Foundation | RRID: CVCL_FA03 |
Human iPSC ALS-TARDBP M337V (CiRA00026) (female, age: 62) | Cell Bank Riken BioResource Research Center | RRID: CVCL_T783 (Egawa et al., 2012) |
Human iPSC ALS-TARDBP A382T (male, age: 50) | Alessandro Rosa Laboratory | Lenzi et al., 2015 |
Human iPSC ALS-C9ORF72 HRE 1 (female, age: 56) | This paper | N/A |
Human iPSC ALS-C9ORF72 HRE 2 (male, age: 59) | This paper | N/A |
Human iPSC ALS-C9ORF72 HRE 3 (male, age: 52) | This paper | N/A |
Human iPSC ALS-SOD1 1 (G93A) (male, age: 47) | This paper | N/A |
Human iPSC ALS-SOD1 2 (I114T) (sex: male, age: 62) | This paper | N/A |
Human iPSC ALS-SOD1 3 (G85S) (sex: female, age: 29) | This paper | N/A |
Mouse primary bone marrow-derived macrophages (WT) (sex: male, age d150) | This paper | N/A |
Mouse primary bone marrow-derived macrophages (Prp-TDP-43Tg/+) (sex: male, age d150) | This paper | N/A |
Experimental Models: Organisms/Strains | ||
Mouse: C57BL/6J (WT) | Jackson Laboratory | Cat# 000664 |
Mouse: B6.Cg-Tg(Prnp-TARDBP∗A315T)95Balo/J (Prp-TDP-43Tg/+) | Jackson Laboratory | Cat# 010700 |
Mouse: Prp-TDP-43Tg/+ x Sting+/− | This paper | N/A |
Mouse: Prp-TDP-43Tg/+ x Sting−/− | This paper | N/A |
Oligonucleotides | ||
Genotyping: Human TARDBP (A315T) forward | https://www.jax.org/Protocol?stockNumber=010700&protocolID=26362 | GGATGAGCTGCGGGAGTTCT |
Genotyping: Human TARDBP (A315T) reverse | https://www.jax.org/Protocol?stockNumber=010700&protocolID=26362 | TGCCCATCATACCCCAACTG |
Genotyping: Mouse Sting forward | This paper | GCTGGGAATTGAACGTAGGA |
Genotyping: Mouse Sting reverse | This paper | GAGGAGACAAAGGCAAGCAC |
Genotyping: Mouse Sting KO forward | This paper | GTGCCCAGTCATAGCCGAAT |
Human TARDBP A315T mutagenesis forward | This paper | GGATTAATGCTGAA CGTACCAAAGTTCATCCCACCA |
Human TARDBP A315T mutagenesis reverse | This paper | TGGTGGGATGAACT TTGGTACGTTCAGCATTAATCC |
Human TARDBP Q331K mutagenesis forward | This paper | CCCCAACTGCTCTT TAGTGCTGCCTGGGC |
Human TARDBP Q331K mutagenesis reverse | This paper | GCCCAGGCAGCACT AAAGAGCAGTTGGGG |
Human STING sgRNA forward | This paper | AGAGCACACTCTCCGGTACC |
Human STING sgRNA reverse | This paper | GGTACCGGAGAGTGTGCTCT |
Mouse Ppid sgRNA forward | This paper | CGTGCCAAAGACTGCAGGTA |
Mouse Ppid sgRNA reverse | This paper | TACCTGCAGTCTTTGGCACG |
qPCR: Human IFNB1 forward | Balka et al., 2020 | TGTCGCCTACTACCTGTTGTGC |
qPCR: Human IFNB1 reverse | Balka et al., 2020 | AACTGCAACCTTTCGAAGCC |
qPCR: Human TNF forward | Balka et al., 2020 | TCTCTCAGCTCCACGCCATT |
qPCR: Human TNF reverse | Balka et al., 2020 | CCCAGGCAGTCAGATCATCTTC |
qPCR: Human MNX1 forward | This paper | GCACCAGTTCAAGCTCAAC |
qPCR: Human MNX1 reverse | This paper | GCTGCGTTTCCATTTCATCC |
qPCR: Human CHAT forward | This paper | AGCCTCATCTCTGGTGTACTC |
qPCR: Human CHAT reverse | This paper | GCCCATAGTATTGCTTCATGC |
qPCR: Human HPRT forward | Balka et al., 2020 | TCAGGCAGTATATCCAAAGATGGT |
qPCR: Human HPRT reverse | Balka et al., 2020 | AGTCTGGCTTATATCCAACACTTCG |
qPCR: Mouse Ifnb1 forward | Balka et al., 2020 | CCAGCTCCAAGAAAGGACGA |
qPCR: Mouse Ifnb1 reverse | Balka et al., 2020 | TGGATGGCAAAGGCAGTGTA |
qPCR: Mouse Ifna6 forward | This paper | GCTTTCCTGATGGTTTTGGTG |
qPCR: Mouse Ifna6 reverse | This paper | AGGCTTTCTTGTTCCTGAGG |
qPCR: Mouse Ifit1 forward | This paper | AGAGTCAAGGCAGGTTTCTG |
qPCR: Mouse Ifit1 reverse | This paper | TGTGAAGTGACATCTCAGCTG |
qPCR: Mouse Mx1 forward | This paper | GATCCGACTTCACTTCCAGATGG |
qPCR: Mouse Mx1 reverse | This paper | CATCTCAGTGGTAGTCAACCC |
qPCR: Mouse Irf7 forward | This paper | AAGCTGGAGCCATGGGTATG |
qPCR: Mouse Irf7 reverse | This paper | CGATGTCTTCGTAGAGACTGTTGG |
qPCR: Mouse Tnf forward | Balka et al., 2020 | CCAAATGGCCTCCCTCTCAT |
qPCR: Mouse Tnf reverse | Balka et al., 2020 | TGGTGGTTTGCTACGACGTG |
qPCR: Mouse Il1b forward | Balka et al., 2020 | TTGACGGACCCCAAAAGATG |
qPCR: Mouse Il1b reverse | Balka et al., 2020 | CAGCTTCTCCACAGCCACAA |
qPCR: Mouse Il6 forward | Balka et al., 2020 | CCAGAAACCGCTATGAAGTTCC |
qPCR: Mouse Il6 reverse | Balka et al., 2020 | CGGACTTGTGAAGTAGGGAAGG |
qPCR: Mouse Hprt forward | Balka et al., 2020 | TGAAGTACTCATTATAGTCAAGGGCA |
qPCR: Mouse Hprt reverse | Balka et al., 2020 | CTGGTGAAAAGGACCTCTCG |
DNA assay: Human MT-ND1 forward | This paper | CTCTTCGTCTGATCCGTCCT |
DNA assay: Human MT-ND1 reverse | This paper | TGAGGTTGCGGTCTGTTAGT |
DNA assay: Human MT-ND2 forward | This paper | GTAGACAGTCCCACCCTCAC |
DNA assay: Human MT-ND2 reverse | This paper | TTGATCCCGTTTCGTGCAAG |
DNA assay: Human POLG1 forward | This paper | CTGCCATAAGGTCTGCAGGT |
DNA assay: Human POLG1 reverse | This paper | CTCCTTTCCGTCAACAGCTC |
DNA assay: Human L1ORF1 gDNA forward | Papasotiriou et al., 2017 | AGAACGCCACAAAGATACTCCTCG |
DNA assay: Human L1ORF1 gDNA reverse | Papasotiriou et al., 2017 | CTCTCTTCTGGCTTGTAGGGTTTCTG |
DNA assay: Mouse Nd1 forward | White et al., 2014 | CAAACACTTATTACAACCCAAGAACA |
DNA assay: Mouse Nd1 reverse | White et al., 2014 | TCATATTATGGCTATGGGTCAGG |
DNA assay: Mouse Nd2 forward | White et al., 2014 | CCATCAACTCAATCTCACTTCTATG |
DNA assay: Mouse Nd2 reverse | White et al., 2014 | GAATCCTGTTAGTGGTGGAAGG |
DNA assay: Mouse L1 gDNA forward | Newman et al., 2012 | TAGGAAATTAGTTT GAATAGGTGAGAGGGT |
DNA assay: Mouse L1 gDNA reverse | Newman et al., 2012 | TCCAGAAGCTGTCAGGTTCTCTGGC |
DNA assay: RNA18S gDNA forward | Chang et al., 2013 | GTAACCCGTTGAACCCCATT |
DNA assay: RNA18S gDNA reverse | Chang et al., 2013 | CCATCCAATCGGTAGTAGCG |
Recombinant DNA | ||
pSLIK-Neo | Aaron D. Gitler Laboratory | Armakola et al., 2012 |
pSLIK-hTDP-43 | Aaron D. Gitler Laboratory | Armakola et al., 2012 |
pSLIK-hTDP-43 Q331K | Aaron D. Gitler Laboratory | Armakola et al., 2012 |
pGW1-hTDP-43-EGFP | Steven Finkbeiner Laboratory | Armakola et al., 2012 |
pGW1-hTDP-43 A315T-EGFP | This paper | N/A |
pGW1-hTDP-43 Q331K-EGFP | This paper | N/A |
pMIH-FLAG-mmcGAS | Benjamin Kile Laboratory | White et al., 2014 |
Software and Algorithms | ||
Fiji | https://fiji.sc/ | RRID: SCR_002285 |
Image Lab | https://www.bio-rad.com/en-us/sku/1709690-image-lab-software | RRID: SCR_014210 |
Prism 8 | https://www.graphpad.com/ | RRID: SCR_002798 |
Imaris | https://imaris.oxinst.com/packages | RRID: SCR_007370 |
Adobe Illustrator | https://www.adobe.com/products/illustrator.thml | RRID: SCR_010279 |
CaseViewer | https://www.3dhistech.com/solution/caseviewer/ | RRID: SCR_017654 |
FlowJo v.10 | https://www.flowjo.com/solutions/flowjo | RRID: SCR_008520 |
MouseMove | Samson et al., 2015 | N/A |