biostudies-literatureKlughammer JConquer Cancer Foundation (Conquer Cancer Foundation of the American Society of Clinical Oncology)Human Frontier Science ProgramThe Cancer Couch Foundation; Catholic Health Foundation; Friends of Dana-Farber Cancer Institute; Hope Scarves; Jamieson Family Fund for Early Career Breast Cancer Researchers; Saverin Family FundHoward Hughes Medical InstituteTerri Brodeur Breast Cancer FoundationEuropean Molecular Biology Organization (EMBO)U.S. Department of Health & Human Services | National Institutes of Health (NIH)Else Kröner-Fresenius-StiftungEuropean Molecular Biology OrganizationElse Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)Lisa Yang; John DoerrNCI NIH HHSHuman Frontier Science Program (HFSP)Conquer Cancer FoundationU.S. Department of Health & Human Services | National Institutes of Health3236-3249https://www.ebi.ac.uk/biostudies/studies/S-EPMC11564109biostudies-literatureUnknown30(11)Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used Nature medicineA multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features.PMC115641092019_A70HHSN261201500003ILT000452/2019-LALTF 738-20171P50CA168504HHSN261100039 / HHSN2612015000017095HHSN261201500003CP50 CA168504Wu JSinha AInga SFiles JMoriel NZhang DAshenberg OWagle NThorner ARHelvie KAlon SNapolitano STolaney SMMurray ESlyper MPatel MGomez Tejeda Zanudo JRozenblatt-Rosen OLako AChen JJohnson BEChen FCaraccio CKanodia AWiner EPBoyden ESMages SNolan GPDionne DFrangieh AWakiro IGoltsev YHughes MERotem ACullen NKlughammer JAbravanel DLGoodwin DRDelloStritto LKBlosser TRTurner MNitzan MPorter CBMOrtiz RRodig SJCohen OSegerstolpe AWaldman JZhuang XNguyen KMacKichan CStrauss SRegev ACui YStrasser RJane-Valbuena JLin NUPfaff KLVigneau SfalseA multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features.Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used 2024-01-01T00:00:00Z2024 Nov2025-07-07T03:09:01.962Z2025-04-05T18:41:01.704ZS-EPMC115641093947811110.1038/s41591-024-03215-z