library_construction_protocol: B6.Ldlr-/- mice underwent a BM transplantation and were fed a WD or normal chow as described above. Single cell RNA-seq was performed as described (34). After euthanasia, aortas were collected, and in some instances, 2 aortas were pooled to generate 1 replicate for single cell analysis. Aortas were minced and digested for 90 minutes at 37°C under agitation in RPMI containing 450 U/ml collagenase I (Sigma-Aldrich, #C0130), 125 U/ml Collagenase XI (Sigma-Aldrich, C7657), 60 U/ml Hyaluronidase (Sigma-Aldrich, H3506), 60 U/ml DNAse (Roche #11284932001), washed in PBS/1% FCS and passed through a 70 μm cell strainer to generate aortic cell suspensions. Cell suspensions were incubated for 5 minutes on ice with TruStain FcX™ (anti-mouse CD16/32, Biolegend #101320, 10 μg/ml), and then labelled with anti-CD45.2-Alexa488 (clone 104, 2 μg/ml, Biolegend #109816), Fixable Viability Dye e780 (ThermoFisher #65-0865-14, 1:1000) and anti-mouse TotalSeqA-Hashtag Antibodies 1 to 15 (1:250 dilution; all from BioLegend, TotalSeq™-A anti-mouse Hashtag antibodies) as follows: hashtag 1 to 4: BMT WD; hashtag 5-8: BM WD. (Hashtag 9-12 refer to samples not included in this study). After 25 minutes incubation at 4°C, cells were washed twice in PBS + 1% FCS and pooled. Viable CD45.2-APC(i.v.)neg CD45.2-Alexa488+ were sorted using a FACS Aria III (BD Biosciences) with a 100μm nozzle. In this experiment, cells were labelled post-sort with a panel of TotalSeq-A CITE-seq antibodies against surface markers, but due to technical issues with the preparation of the CITE-seq cDNA library, the CITE-seq results are not interpretable. Cells were washed twice with PBS supplemented with 0.04% ultrapure BSA (Thermofisher AM2616), counted and loaded in the 10x Genomics Chromium with the aim to recover 10,000 cells. Single cells were encapsulated into droplets with the Chromium™ Controller (10x Genomics). Transcripts captured in all cells encapsulated with a bead were uniquely barcoded using a combination of a 16 bp 10x Barcode and a 12 bp unique molecular identifier (UMI). cDNA libraries were generated using the Chromium™ Single Cell 3' Library & Gel Bead Kit v3 (10x Genomics) following the detailed protocol provided by the manufacturer. -CITE-seq library: amplification was performed at 95°C for 3' followed by ten cycles at 95°C f¬¬or 20''; 60°C for 30''; 72°C for 20'' and final elongation 72°C for 5' with 5'-CAAGCAGAAGACGGCATACGAGATCGTGATGTGACTGGAGTTCCTTGGCACCCGAGAATTCCA-3' Small RNA RPI1 primer as i7 primer (Illumina). -HASH-seq library: amplification was performed at 95°C for 3' followed by ten cycles 95°C for 20''; 64°C for 30''; 72°C for 20'' and final elongation 72°C for 5' with 5'-CAAGCAGAAGACGGCATACGAGATCGAGTAATGTGACTGGAGTTCAGACGTGTGC-3' TruSeq D701_s primer as i7 primer (Illumina). The following 5'- AATGATACGGCGACCACCGAGATCTACACTCTTTCCCTACACGACGCTC-3' SI-PCR primer as i5 primer (Illumina) was used for HASH- seq library amplification. Following the final bead purification, all three libraries were pooled as 80% mRNA library, 10% ADT library and 10% HTO library before sequencing.