Key resources table
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Guinea pig polyclonal anti-Insulin | Abcam | Cat# ab7842; RRID: AB_306130 |
| Purified Mouse monoclonal anti-Ki67 (clone B56) | BD Biosciences | Cat# 550609; RRID: AB_393778 |
| Rabbit polyclonal anti-phopho-Histone H3 (Ser10) | Millipore | Cat# 06-570; RRID: AB_310177 |
| Mouse monoclonal anti-Elastase 3A (clone 14-3) | Santa Cruz Biotechnology | Cat# sc-100527; RRID: AB_628381 |
| Rabbit polyclonal anti-CELA3B(N-terminal) | Sigma | Cat# SAB1306246 |
| Mouse monoclonal anti-E-Cadherin (clone 4A2) | Cell Signaling Technology | Cat# 14472; RRID: AB_2728770 |
| Recombinant Rabbit monoclonal anti-glucagon (clone EP3070) | Abcam | Cat# ab92517; RRID: AB_10561971 |
| Mouse monoclonal anti-ELA3B (clone 3H3) | Sigma | Cat# SAB1409028; RRID: |
| Mouse monoclonal anti-trypsin (clone D-1) | Santa Cruz Biotechnology | Cat# sc-137077, RRID:AB_2300318 |
| Mouse monoclonal anti-Amylase | Santa Cruz Biotechnology | Cat# sc-46657, RRID:AB_626668 |
| Rabbit monoclonal anti-PDX1 (D59H3) | Cell Signaling Technology | Cat# 5679; RRID: AB_10706174 |
| Mouse monoclonal anti-PAR2 (SAM11) | Thermo Fisher | Cat# 35-2300; RRID: AB_2533199 |
| Mouse monoclonal anti-PAR3 (G-4) | Santa Cruz Biotechnology | Cat# sc-393127 |
| Rabbit polyclonal anti-FAK | Cell Signaling Technology | Cat# 3285; RRID: AB_2269034 |
| Rabbit polyclonal anti-phopsho PAK1 (Ser144)/PAK2 (Ser141) | Cell Signaling Technology | Cat# 2606; RRID: AB_2299279 |
| Rabbit polyclonal anti-PAK1/2/3 | Cell Signaling Technology | Cat# 2604; RRID: AB_2160225 |
| Rabbit polyclonal anti-phopsho p44/42 MAPK (Erk 1/2) (Thr202/Tyr204) | Cell Signaling Technology | Cat# 9101; RRID: AB_331646 |
| Rabbit polyclonal anti-p44/42 MAPK (Erk 1/2) | Cell Signaling Technology | Cat# 9102; RRID: AB_320744 |
| Rabbit monoclonal anti-β-actin (13E5) | Cell Signaling Technology | Cat# 4970; RRID: AB_2223172 |
| Mouse monoclonal anti-Vinculin (7F9) | Santa Cruz Biotechnology | Cat# sc-73614; RRID: AB_1131294 |
| Rabbit monoclonal anti-GAPDH (D16H11) | Cell Signaling Technology | Cat# 5174; RRID: AB_10622025 |
| APC Annexin V | BD Biosciences | Cat# 550474; RRID: AB_2868885 |
| Bacterial and virus strains | ||
| N/A | ||
| Biological samples | ||
| Human islets | IIDP/Prodo Labs | Table S1 |
| Human acinar cells | Prodo Labs | |
| Human ductal cells | Prodo Labs | |
| Human pancreatic sections | nPOD | |
| Human bone marrow Total RNA | Takara | Cat# 636591 |
| Chemicals, peptides, and recombinant proteins | ||
| TRIzol Reagent | Thermo Fisher | Cat# 15596018 |
| Pierce RIPA buffer | Thermo Fisher | Cat# 89901 |
| Performer Set | Broad Institute | Wawer et al., 2014 1 |
| Informer Set | Broad Institute | Chen et al., 2005; Tan, 20052 |
| Repurpose Set | Broad Institute | Corsello et al., 2017 3 |
| Telaprevir | Selleckchem | Cat# S1538 |
| Sivelestat | Selleckchem | Cat# S4666 |
| Tebipenem Pivoxil | Selleckchem | Cat# S2159 |
| Human pancreatic elastase | Elastin Product Company | Cat# HE145 |
| Porcine pancreatic elastase | Elastin Product Company | Cat# ES438 |
| Human neutrophil elastase | Elastin Product Company | Cat# SE563 |
| Human cathepsin G | Elastin Product Company | Cat# SG623 |
| N-Methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide | Sigma | Cat# M4765 |
| N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide | Elastin Product Company | Cat# SG554 |
| FSSLRY-NH2 | Tocris | Cat# 4751 |
| 4-Hydroxytamoxifen (4-OHT) | Sigma | Cat# H6278 |
| Elastase 3B (ELA3B) recombinant protein | MyBioSource | Cat# MBS2012053 |
| DA-ZP1 | From Dr. Amit Choudhary | Lee et al., 2020 4 |
| Critical commercial assays | ||
| Caspase-3/CPP32 Colorimetric assay kit | Biovision | Cat# K106 |
| Click-iT Plus EdU Alexa Fluor™ 488 Flow Cytometry Assay Kit | Thermo Fisher | Cat# C10632 |
| Click-iT Plus EdU Alexa Fluor™ 647 Flow Cytometry Assay Kit | Thermo Fisher | Cat# C10634 |
| eBioscience Annexin V Apoptosis Detection Kit APC | Thermo Fisher | Cat# 88-8007-72 |
| ApopTag Fluorescein In Situ Apoptosis Detection Kit | Sigma | Cat# S7110 |
| EnzCheck Elastase Assay kit | Thermo Fisher | Cat# E-12056 |
| Phopsho-antibody microarray | Kinexus | Cat# KAM-1325 |
| Chromium Single Cell 3’ Library & Gel Bead Kit v2 | 10x Genomics | Cat# PN-120237 |
| Chromium Single Cell A Chip Kit | 10x Genomics | Cat# PN-120236 |
| Chromium i7 Sample index plate | 10x Genomics | Cat# PN-220103 |
| Dead cell removal kit | Miltenyi Biotec | Cat# 130-090-101 |
| Insulin Human ELISA kit | Mercodia | Cat# 10-1113-01 |
| C-peptide Human ELISA kit | Mercodia | Cat# 10-1136-01 |
| Mouse C-peptide ELISA kit | Crystal Chem | Cat# 90050 |
| Deposited data | ||
| Single-cell RNA-seq dataset | This paper | GSE190447 |
| Phospho-antibody microarray dataset | This paper | GSE189986 |
| Experimental models: Cell lines | ||
| EndoC-βH1 | Human Cell Design | RRID: CVCL-L909 |
| EndoC-βH3 | Human Cell Design | RRID: CVCL-IS72 |
| Experimental models: Organisms/strains | ||
| Tg(ins:FLAG-NTR,cryaa:mCherry) s950 | From Dr. Olov Andersson | Andersson et al., 20125 |
| Tg(EPV.Tp1-Mmu.Hbb:hist2h2l-mCherry) s939 | From Dr. Olov Andersson | Ninov et al., 20126 |
| Tg(ins:flag-NTR);Tg(tp1:H2BmCherry) | From Dr. Olov Andersson | Lu et al., 2016 7 |
| C57BL/6J | Jackon lab | Cat#:000664 RRID:IMSR_JAX:00 0664 |
| NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ | Jackson lab | Cat#:005557 RRID:IMSR_JAX:00 5557 |
| Oligonucleotides | ||
| RT-PCT oligonucleotides | IDT | Table S2 |
| ON-TARGETplus Human PTK2 siRNA pool | Dharmacon | Cat# L-003164-00-0010 |
| ON-TARGETplus Non-targeting siRNA pool | Dharmacon | Cat# D-001810-10-20 |
| Recombinant DNA | ||
| pReceiver-M35 | Genecopoeia | Cat# EX-NEG-M35-B |
| ORF Clone PTK2 | Genecopoeia | Cat# EX-I0314-M35-B; NM_153831.3 |
| Software and algorithms | ||
| Cellranger version 6.0.0 | 10x Genomics | https://support.10xgenomics.com/single-cell-gene-expression/software/downloads/latest;RRID:SCR_017344 |
| Differential gene expression analysis of microarrays: limma | https://bioconductor.org/packages/release/; Ritchie et al., 20158 | RRID:SCR_010943 |
| Differential gene expression analysis of RNAseq: edgeR | https://bioconductor.org/packages/release/; Robinson et al., 20109 | RRID:SCR_012802 |
| ImageJ | http://imagej.net/Contributors; | RRID: SCR_003070 |
| QuPath | https://qupath.github.io ; Bankhead et al., 201710 | RRID:SCR_018257 |
| GraphPad Prism v9.5.1 | www.graphpad.com/ | RRID:SCR_002798 |
| Scater | https://bioconductor.org/packages/release/bioc/html/scater.html | RRID:SCR_015954 |
| Other | ||
| RNeasy Mini Kit | Qiagen | Cat# 74106 |
| Lipofectamine 3000 Transfection reagent | Invitrogen | Cat# L3000001 |
| Lipofectamine RNAiMax Transfection reagent | Invitrogen | Cat# 13778075 |
| Annexin V Binding Buffer, 10X concentrate | BD Biosciences | Cat# 556454 |
| Bio-Gel P-4 Gel | Bio-Rad | Cat# 1504124 |
| Osmotic mini pumps | Alzet | Cat# 1004 |
| High-Capacity cDNA Reverse Transcription Kit | Applied Biosystems | Cat# 4368814 |
| Low Fat Diet (10%) | Research Diet | Cat# D12450K |
| High Fat Diet (60%) | Research Diet | Cat# D12492 |