REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit anti-Phospho-S6 Ribosomal	Cell Signaling Technology	Cat. No. 4856; RRID: AB_2181037
Goat anti-Rabbit IgG (Alexa Fluor 647)	Thermo Fisher	Cat. No. A-21245; RRID: AB_2535813
Biological Samples
Fetal Bovine Serum	Biological Industries	Cat. No. 04-005-1A
Chemicals, Peptides, and Recombinant Proteins
O.C.T. Compound Cryostat Embedding Medium	Scigen	Cat. No. 4586
Poly-L-lysin solution	Sigma-Aldrich	Cat. No. P8920
Formaldehyde, 37% (w/v)	J.T. Baker	Cat. No. JT2106
PBS, pH 7.4, RNase-free, 10 ×	Ambion	Cat. No. AM9625
Water UltraPure Dnase/RNase-free Molecular Biology	Bio-Lab	Cat. No. 23217723
Proteinase K	Ambion	Cat. No. AM2546
Formamide, deionized, nuclease-free	Ambion	Cat. No. AM9342
Dextran sulfate	Sigma-Aldrich	Cat. No. D8906
E.coli tRNA, Roche	Sigma-Aldrich	Cat. No. R1753
BSA	Ambion	Cat. No. AM2616
Vanadyl- ribonucleoside complex	NEB	Cat. No. S1402S
Cy5 Mono-Reactive Dye Pack	Sigma-Aldrich	Cat. No. PA25001
6-TMRA, SE	Thermo Fisher	Cat. No. C6123
Alexa Fluor 594 carboxylic acid, succinimidyl ester	Thermo Fisher	Cat. No. A20004
DAPI	Sigma-Aldrich	Cat. No. D9542
Alexa Fluor 488 Phalloidin	Thermo Fisher	Cat. No. A12379
ProLong Gold Antifade Mountant	Molecular Probes	Cat. No. P36934
CAS block	Thermo Fisher	Cat. No. 008120
TRI reagent	Sigma-Aldrich	Cat. No. T9424
(Tyr[SO3H]27) Cholecystokinin fragment 26-33 Amide	Sigma-Aldrich	Cat. No. C2175
Insulin	Sigma-Aldrich	Cat. No. I1882
Maxima H -RT	Thermo Fisher	Cat. No. EP0753
dNTPs	Thermo Fisher	Cat. No. R0182
PEG 8000	Sigma-Aldrich	Cat. No. 89510
Exonuclease I	Thermo Fisher	Cat. No. EN0582
AM pure beads	Beckman Coulter	Cat. No. A63881
Terra direct polymerase	Clontech	Cat. No. 639270
Critical Commercial Assays
Direct-zol RNA Miniprep kit	Zymo Research	Cat. No. R2050
Nextera XT DNA Library Prep Kit	Illumina	Cat. No. FC-131-1024
NextSeq 500 Kits v2 (75 cycles)	Illumina	Cat. No. FC-404-2005
Deposited Data
RNA sequencing of AR42J cells	This paper	GEO: GSE154533
Islet isolation data	Neelankal John et al., 2018	GEO: GSE107489
Islet isolation data	Jaafar et al., 2019	GEO: GSE132261
Tabula Muris dataset	Tabula Muris Consortium, 2018	https://tabula-muris.ds.czbiohub.org/; GEO: GSE109774
Matrisome components data	Naba et al., 2016	http://matrisomeproject.mit.edu/
Ligand-receptor data	Ramilowski et al., 2015	https://doi.org/10.1038/ncomms8866
Experimental Models: Cell Lines
AR42J	James Dutton	https://www.atcc.org/products/all/CRL-1492.aspx RRID:CVCL_0143
Experimental Models: Organisms/Strains
B6.BKS(D)-Leprdb/J mice on C57BL/6J genetic background	The Jackson Laboratory	Strain: 000697 | B6 db
BKS.Cg-Dock7m +/+ Leprdb/J on C57BLKS/J genetic background	The Jackson Laboratory	Strain: 000642| BKS db
C57BL/6J mice	The Jackson Laboratory	Strain: 000664 | B6/J
C57BL/6 mice	Envigo	Strain: C57BL/6JOlaHsd
Oligonucleotides
smFISH probes, see Table S4	This paper	N/A
SINGV6 primer: /5Biosg/ACA CTC TTT CCC TAC ACG ACG C	IDT (Standard Desalting)	N/A
barcoded RT primer	Bagnoli et al., 2018 (Standard Desalting)	N/A
TSO∗ E5V6NEXT: ACA CTC TTT CCC TAC ACG ACG CrGrG rG	IDT (RNA oligo RNase Free HPLC Purification)	N/A
P5NEXTPT5: AAT GAT ACG GCG ACC ACC GAG ATC TAC ACT CTT TCC CTA CAC GAC GCT CTT CCG∗ A∗T∗C∗ T	IDT (HPLC purification)	N/A
Software and Algorithms
Stellaris FISH Probe Designer	Biosearch Technologies, Inc., Petaluma, CA	https://biosearchtech.com/products/rna-fish/
R and RStudio v3.6.1	R Consortium	https://rstudio.com/
MATLAB R2016b	MathWorks	https://www.mathworks.com/
ImageM	Lyubimova et al., 2013	N/A
ImageJ 1.52d	Schindelin et al., 2012	https://imagej.nih.gov/ij/; RRID:SCR_003070
MetaMorph software	Molecular Devices, Downington, PA	https://www.biocompare.com/19333-Image-Analysis-Software-Image-Processing-Software/78845-MetaMorphreg-Microscopy-Automation-Image-Analysis-Software/
NIS-Elements software	Nikon Instruments, Melville, NY	https://www.nikon.com/products/microscope-solutions/lineup/img_soft/nis-elements/
edgeR version 3.26.8	Robinson et al., 2010	N/A
bcl2fastq	Illumina	https://support.illumina.com/sequencing/sequencing_software/bcl2fastq-conversion-software.html RRID: SCR_015058
zUMI package	Parekh et al., 2018	N/A