Methods and applications for single-cell and spatial multi-omics

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 494 - 515

Published: March 2, 2023

Language: Английский

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Liver tumour immune microenvironment subtypes and neutrophil heterogeneity

Nature, Journal Year: 2022, Volume and Issue: 612(7938), P. 141 - 147

Published: Nov. 9, 2022

Language: Английский

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Gut-liver axis: Pathophysiological concepts and clinical implications

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1700 - 1718

Published: Oct. 7, 2022

Language: Английский

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Macrophage diversity in cancer revisited in the era of single-cell omics

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 546 - 563

Published: June 9, 2022

TAMs have diverse functions in cancer, reflecting the heterogenous nature of these immune cells. Here, we propose a new nomenclature to identify TAM subsets.Recent single cell multi-omics technologies, which allow clustering subsets an unbiased manner, significantly advanced our understanding molecular diversity mice and humans.Novel mechanisms potential therapeutic targets been identified that might regulate tumor-promoting function different subsets.TAM opens promising opportunities for envisaging putative cancer treatments. Tumor-associated macrophages (TAMs) multiple potent and, thus, represent important targets. These highlight TAMs. Recent omics technologies However, unifying annotation their signatures is lacking. review recent major studies transcriptome, epigenome, metabolome, spatial with specific focus on We also consensus model present avenues future research. one most abundant types tumors [1.Cassetta L. Pollard J.W. Targeting macrophages: approaches cancer.Nat. Rev. Drug Discov. 2018; 17: 887-904Crossref PubMed Scopus (650) Google Scholar]. Since initial decade ago [2.Qian B.Z. Macrophage enhances tumor progression metastasis.Cell. 2010; 141: 39-51Abstract Full Text PDF (3151) Scholar], functional now widely appreciated, many seminal field [3.Yang M. et al.Diverse microenvironments.Cancer Res. 78: 5492-5503Crossref (202) Scholar, 4.DeNardo D.G. Ruffell B. Macrophages as regulators tumour immunity immunotherapy.Nat. Immunol. 2019; 19: 369-382Crossref (643) 5.Lopez-Yrigoyen al.Macrophage targeting cancer.Ann. N. Y. Acad. Sci. 2021; 1499: 18-41Crossref (25) This array includes promotion growth, lineage plasticity, invasion, remodeling extracellular matrix, crosstalk endothelial, mesenchymal stromal cells, other cells; effects can result progression, metastasis (see Glossary), therapy resistance [6.Mantovani A. al.Tumour-associated treatment oncology.Nat. Clin. Oncol. 2017; 14: 399-416Crossref (1675) Scholar,7.Guc E. Redefining macrophage neutrophil biology metastatic cascade.Immunity. 54: 885-902Abstract (13) With wide application years seen explosion data illustrating cellular heterogeneity resulting unprecedented amount information TAMs, regardless main studies. Links between are emerging. terminology lacking, making direct comparisons full utilization sets difficult. In this review, summarize human data; include traditional nomenclatures, at levels single-cell transcriptomic, epigenomic, metabolic multi-omics, opportunities, directions. subsets. hope will serve starting point help build complete picture dynamic interactions tumor, well microenvironment (TME). A used describe has now-obsolete M1/M2 model, proposed ~20 ago; it separated into two distinct arms: M1 or 'classically' activated; M2 'alternatively' activated, largely based vitro stimulating type 1 2 cytokines [8.Mills C.D. al.M-1/M-2 Th1/Th2 paradigm.J. 2000; 164: 6166-6173Crossref The newer term 'M1-like' phenotype typically described proinflammatory induced by Toll-like receptor (TLR) ligands cytokines, namely IFN-γ TNF-α. Conversely, 'M2-like' having anti-inflammatory characteristics, being activated interleukin (IL)-4 IL-13, producing TGF-β profibrotic factors. nomenclature, albeit used, remains oversimplified [9.Martinez F.O. Gordon S. paradigm activation: time reassessment.F1000Prime Rep. 2014; 6: 13Crossref (2673) Scholar,10.Nahrendorf Swirski F.K. Abandoning network function.Circ. 2016; 119: 414-417Crossref (195) Indeed, significant morphology, function, surface marker expression observed resident-tissue (RTMs) from organs [11.Bleriot C. al.Determinants resident tissue identity function.Immunity. 2020; 52: 957-970Abstract (94) Scholar]; moreover, co-expression both gene almost all [12.Mulder K. al.Cross-tissue landscape monocytes health disease.Immunity. 1883-1900Abstract Therefore, spectrum polarization relates represents more sensible approach describing [10.Nahrendorf Scholar,13.Mosser D.M. Edwards J.P. Exploring activation.Nat. 2008; 8: 958-969Crossref (5864) normal homeostasis, tightly regulated niche-like local environment, recently [14.Guilliams al.Establishment maintenance niche.Immunity. 434-451Abstract (138) Another layer derives origin. Using lineage-tracing mice, illustrated mouse RTMs derived early erythromyeloid progenitors formed either yolk sac fetal liver [15.Geissmann F. al.Blood consist principal migratory properties.Immunity. 2003; 71-82Abstract (2514) Scholar,16.Gomez Perdiguero al.Tissue-resident originate yolk-sac-derived erythro-myeloid progenitors.Nature. 2015; 518: 547-551Crossref (1236) Additionally, adult may derive circulating monocytic precursors (monocytes) bone marrow [17.Cox al.Origins, biology, diseases macrophages.Annu. 39: 313-344Crossref (1) monocyte contribution varies among organs. For example, steady state, microglia central nervous system (CNS) solely [18.Hoeffel G. al.C-Myb(+) progenitor-derived give rise tissue-resident macrophages.Immunity. 42: 665-678Abstract (611) while dermal embryonic origin [19.Kolter J. al.A subset skin contributes surveillance regeneration nerves.Immunity. 50: 1482-1497Abstract (69) appreciated repeatedly reviewed [20.Pathria P. al.Targeting tumor-associated cancer.Trends 40: 310-327Abstract (382) Scholar,21.Guerriero J.L. Macrophages: road less traveled, changing anticancer therapy.Trends Mol. Med. 24: 472-489Abstract (143) Similar counterparts not only its ontogeny, but cues, including type, organ, subanatomic Identifying basis over past [5.Lopez-Yrigoyen advancements unveiling multidimensional complexity manner. research, oncology eventually fully understand cells hopefully use improve precision diagnosis therapy. Single RNA sequencing (scRNA-seq) technology revolutionized providing in-depth transcriptome level [22.Giladi al.Single-cell characterization haematopoietic trajectories homeostasis perturbed haematopoiesis.Nat. Cell Biol. 20: 836-846Crossref (139) substantial advances available experimental techniques bioinformatics pipelines years, scRNA-seq investigate [23.Lawson D.A. al.Tumour resolution.Nat. 1349-1360Crossref (230) Scholar,24.Ren X. al.Insights gained analysis microenvironment.Annu. 583-609Crossref (15) transcriptomic remain Two large-scale pan-cancer provided valuable regarding diversity. One study analyzed myeloid 380 samples across 15 210 patients through combination newly collected eight published [25.Cheng transcriptional atlas infiltrating cells.Cell. 184: 792-809Abstract (111) Comparison consistent presence CD14+ CD16+ tumor-infiltrating (TIMs), LYVE1+ interstitial non-cancer tissues, seven clusters: INHBA+ C1QC+ ISG15+ LNRP3+ SPP1+ compiled mononuclear phagocytes (MNPs) isolated 41 13 types, six common universe, termed MNP-VERSE. Monocyte clusters were then extracted reintegrated generate MoMac-VERSEi. regulatory inference (SCENIC) [26.Aibar al.SCENIC: clustering.Nat. Methods. 1083-1086Crossref (1003) authors classical monocytes, nonclassical five (HES1 TAM, C1Qhi TREM2 IL4I1 proliferating TAMs) Although nomenclatures studies, others, pattern transcriptomics By reviewing journals, found preserved (Table 1). Based signature genes, enriched pathways, predicated naming interferon-primed (IFN-TAMs), (Reg-TAMs), inflammatory cytokine-enriched (Inflam-TAMs), lipid-associated (LA-TAMs), pro-angiogenic (Angio-TAMs), RTM-like (RTM-TAMs), (Prolif-TAMs) Figure 1, Key figure). Furthermore, three TIMs Box 1).Table 1Mouse various TMEsaBlack font: genes clusters; blue protein markers Underline: CITE-seq; Bold: key reported than paper., bAbbreviations: BRCA, breast cancer; CAF, cancer-associated macrophage; CITE-seq, indexing transcriptomes epitopes sequencing; CRC, colorectal CyTOF, Mass cytometry flight; ECM, matrix; ESCA, esophageal carcinoma; GC, gastric HCC, hepatocellular HNC, head neck i.v., intravenous; IF, immunofluorescent staining; INs-seq, intracellular staining LCM, laser capture microdissection; LYM, lymphoma; MEL, melanoma; Mets, metastasis; mIHC, multiplex immunochemistry MMY, myeloma; N/A, available; NPC, nasopharyngeal NSCLC, nonsmall lung OS, osteosarcoma; OVC, ovarian PDAC, pancreatic ductal adenocarcinoma; PRAC, prostate RCC, renal Reg-TAMs, TAMs; SARC, sarcoma; sc-MS, mass spectrometry; SEPN, spinal ependymomas; SKC, ST, transcriptomics; s.c., subcutaneous; macrophages; THCA, thyroid UCEC, uterine corpus endometrial carcinoma.AnnotationSpeciesSignatureTFCancer typeFunction/enriched pathwayAssayRefsIFN-TAMsHumanCASP1, CASP4, CCL2/3/4/7/8, CD274hi, CD40, CXCL2/3/9/10/11, IDO1, IFI6, IFIT1/2/3, IFITM1/3, IRF1, IRF7, ISG15, LAMP3, PDCD1LG2hi, TNFSF10, C1QA/C, CD38, IL4I1, IFI44LSTAT1 IRF1/7BRCACRCCRC metsGBMHCCHNCLYMMELMMYNPCNSCLCOSPDACSEPNTHCAUCECApoptosis regulatorsEnhance proliferationInflammatory responsesPromote Treg entry tumorT exhaustionImmunosuppressionColocalization exhausted T (ST, IF)Decreased antigen presentation (CyTOF)Suppressed activation (in vitro)IFN-α/γ-IFN response signature; IL2/STAT5; IL6/JAK/STAT3scRNA-seqCITE-seqmIHCSTNanoString GeoMx[12.Mulder Scholar,29.Gubin M.M. al.High-dimensional delineates lymphoid compartment during successful immune-checkpoint therapy.Cell. 175: 1014-1030Abstract (165) Scholar,32.Zavidij O. reveals compromised precursor stages myeloma.Nat. Cancer. 1: 493-506Crossref 33.Zhou intratumoral immunosuppressive osteosarcoma.Nat. Commun. 11: 6322Crossref (74) 34.Zhang Q. al.Interrogation microenvironmental ependymomas dual macrophages.Nat. 12: 6867Crossref (0) Scholar,45.Wu al.Spatiotemporal level.Cancer 134-153Crossref (10) Scholar,52.Pombo Antunes A.R. profiling glioblastoma species disease stage competition specialization.Nat. Neurosci. 595-610Crossref (78) Scholar,\81.Wu S.Z. spatially resolved cancers.Nat. Genet. 53: 1334-1347Crossref (47) Scholar,83.Pelka al.Spatially organized multicellular hubs cancer.Cell. 4734-4752Abstract (29) Scholar]CD14+, CD11b+, CD68+, PD-L1hi, PD-L2hi, CD80hi, CD86hi, MHCIIhi, CD86+, MRC1–, SIGLEC1–, HLA-DRlo, CD314+, CD107a+, CD86, TLR4, CD44 (CITE-seq)MouseCcl2/7/8, Cd274, Cxcl9/10/11, Ifit1/2/3, Ifit3, Ifitm1/3, Il7r, Isg15, Nos2, Rsad2, Tnfsf10, Stat1N/ACT26 s.c. CRCCT26 intrasplenic mets modelT3 SARC (s.c.)Orthotopic GL261 GBMIFN signaturescRNA-seqCITE-seqmIHC[29.Gubin Scholar]Inflam-TAMsHumanCCL2/3/4/5/20, CCL3L1, CCL3L3, CCL4L2, CCL4L4, CXCL1/2/3/5/8, G0S2, IL1B, IL1RN, IL6, INHBA, KLF2/6, NEDD9, PMAIP1, S100A8/A9, SPP1EGR3 IKZF1 NFKB1 NFE2L2 RELCRCCRC metsOSSEPNGCRecruiting regulating cellsCNS inflammation-associated chemokinesPromotes inflammationNeutrophil recruitment lumenT interaction (IHC)TNF signaling; WNTImmune check pointsscRNA-seqmIHCNanoString GeoMx[31.Che L.-H. metastases reprogramming preoperative chemotherapy.Cell Discovery. 7: 80Crossref (4) Scholar,33.Zhou Scholar,34.Zhang Scholar,42.Sathe genomic microenvironment.Clin. Cancer 26: 2640-2653Crossref (66) 43.Zhang al.Dissecting underlying premalignant lesions cancer.Cell 27: 1934-1947Abstract (104) 44.Yin H. map development using sequencing.Front. 12728169Crossref 45.Wu Scholar]MouseCxcl1/2/3/5/8, Ccl20, Ccl3l1, Il1rn, Il1b, G0s2, Inhba, Spp1N/ACT26 CRC CT26 modelChemokine productionImmunosuppressionscRNA-seq[45.Wu Scholar]LA-TAMsHumanACP5, AOPE, APOC1, ATF1, C1QA/B/C, CCL18, CD163, CD36, CD63, CHI3L1, CTSB/D/L, F13A1, FABP5, FOLR2, GPNMB, IRF3, LGALS3, LIPA, LPL, MACRO, MerTK, MMP7/9/12, MRC1, NR1H3, NRF1, NUPR1, PLA2G7, RNASE1, SPARC, SPP1, TFDP2, TREM2, ZEB1FOS/JUN HIF1A MAF/MAFB NR1H3 TCF4 TFECBRCACRCCRC metsGBMGCHCCHNCNPCNSCLCOSPDACPhagocytosisPromotion EMTComplement activationECM degradationAntigen processing pathwaysATP biosynthetic processesCanonical M2-like pathwaysFatty acid metabolismImmunosuppressionInflammationIron ion signalingscRNA-seqSMART-seq2CITE-seqmIHCST[12.Mulder Scholar,27.Zilionis R. cancers conserved populations individuals species.Immunity. 1317-1334Abstract (424) Scholar,28.Yang non-small differences sexes.Front. 12756722Google Scholar,30.Zhang analyses inform myeloid-targeted therapies colon 181: 442-459Abstract (246) Scholar,31.Che Scholar,50.Chen Y.P. subtypes associated prognosis carcinoma.Cell 30: 1024-1042Crossref (71) Scholar,81.Wu Scholar]CD9+, CD80+, MAF, CD163lo/-, CD206+/lo, CD71+, CD72+, CD73, ICOSL, CD40LG, Thy-1 (CITE-seq)MouseAcp5, Apoc1, Apoe, C1qa/B/C, Ccl18, Ccl8, Cd163, Cd206, Cd36, Cd63, Ctsb/d/l, Cxcl9, Fabp5, Folr2, Gpnmb, Lgals3, Macro, Mrc1, Trem2MAFCT26 Orthotopic GBM 7940b orthotopic iKras p53 PDAC metsPhagocytosisAntigen presentationFatty metabolismComplement activationscRNA-seqCITE-seqmIHC[45.Wu Scholar,46.Kemp S.B. al.Pancreatic marked complement-high blood tumor–associated macrophages.Life Alliance. 4e202000935Crossref Scholar]Angio-TAMsHumanADAM8, AREG, BNIP3, CCL2/4/20, CD300E, CD44, CD55, CEBPB, CLEC5A, CTSB, EREG, FCN1, FLT1, FN1, HES1, IL8, MIF, OLR1, PPARG, S100A8/9/12, SERPINB2, SLC2A1, SPIC, THBS1, TIMP1, VCAN, VEGFABACH1 CEBPB FOSL2 HIFA KLF5 MAF RUNX1 SPIC TEAD1 ZEB2BRCACRCCRCCRC metsESCAGBMGCHCCMELNPCNPCNSCLCOVCPDACPDAC metsRCCSEPNTHCAUCECAngiogenesisCAF interactionECM proteolysis; ECM interactionPromotion EMTHIF pathway; NF-kB Notch VEGF signalingJuxtaposed PLVAP+/DLL4+ endothelial (IF)scRNA-seqSMART-seq2CITE-seqNanoString GeoMx[25.Cheng Scholar,41.Sharma al.Onco-fetal drives carcinoma.Cell. 183: 377-394Abstract (103) Scholar,49.Raghavan al.Microenvironment drug 6119-6137Abstract Scholar,67.Zhao revealed promoted progression.J. Transl. 454Crossref Scholar]CD52hi, CD163hi, CD206hi, CXCR4+, CD354+, FOSL2, VEGFAMouseArg1, Adam8, Bnip3, Mif, Slc2a1N/AOrthotopic modelHIF signalingAngiogenesisscRNA-seqCITE-seq[52.Pombo Scholar]Reg-TAMsHumanCCL2, CD274, CD80, CHIT1, CX3CR1, HLA-A/C, HLA-DQA1/B1, HLA-DRA/B1/B5, ICOSLG, IL-10, ITGA4, LGALS9, MAC

Language: Английский

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Macrophages in health and disease

Cell, Journal Year: 2022, Volume and Issue: 185(23), P. 4259 - 4279

Published: Nov. 1, 2022

Language: Английский

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Biology of lung macrophages in health and disease

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1564 - 1580

Published: Sept. 1, 2022

Language: Английский

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Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

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Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

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Hepatic inflammatory responses in liver fibrosis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(10), P. 633 - 646

Published: July 3, 2023

Language: Английский

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Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Science, Journal Year: 2022, Volume and Issue: 376(6594)

Published: May 12, 2022

Understanding gene function and regulation in homeostasis disease requires knowledge of the cellular tissue contexts which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen types from 16 donors 25 samples, generating a cross-tissue atlas 209,126 nuclei profiles, integrated across tissues, donors, laboratory with conditional variational autoencoder. Using resulting atlas, highlight shared tissue-specific features tissue-resident cell populations; identify that might contribute neuromuscular, metabolic, immune components monogenic diseases biological processes involved their pathology; determine modules underlie mechanisms for complex traits analyzed by genome-wide association studies.

Language: Английский

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