دورية أكاديمية

A spatial expression atlas of the adult human proximal small intestine.

التفاصيل البيبلوغرافية
العنوان: A spatial expression atlas of the adult human proximal small intestine.
المؤلفون: Harnik Y; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Yakubovsky O; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.; Department of General Surgery and Transplantation, Sheba Medical Center, Ramat Gan, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Hoefflin R; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Novoselsky R; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Bahar Halpern K; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Barkai T; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.; Sheba Medical Center, Ramat Gan, Israel., Korem Kohanim Y; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Egozi A; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Golani O; Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel., Addadi Y; Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel., Kedmi M; Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel., Keidar Haran T; Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Levin Y; The De Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel., Savidor A; The De Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel., Keren-Shaul H; Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel., Mayer C; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Institute of Pathology, Sheba Medical Center, Ramat Gan, Israel., Pencovich N; Department of General Surgery and Transplantation, Sheba Medical Center, Ramat Gan, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Pery R; Department of General Surgery and Transplantation, Sheba Medical Center, Ramat Gan, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Shouval DS; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel., Tirosh I; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel., Nachmany I; Department of General Surgery and Transplantation, Sheba Medical Center, Ramat Gan, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Itzkovitz S; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. shalev.itzkovitz@weizmann.ac.il.
المصدر: Nature [Nature] 2024 Aug; Vol. 632 (8027), pp. 1101-1109. Date of Electronic Publication: 2024 Aug 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Gene Expression Profiling* , Intestine, Small*/cytology , Intestine, Small*/immunology , Intestine, Small*/metabolism , Cell Biology*, Adult ; Animals ; Female ; Humans ; Male ; Mice ; Cell Movement ; Chylomicrons/biosynthesis ; Enterocytes/metabolism ; Enterocytes/cytology ; Epithelial Cells ; In Situ Hybridization, Fluorescence ; Intestinal Mucosa/cytology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Iron/metabolism ; Lipid Droplets/metabolism ; Macrophages/cytology ; Macrophages/immunology ; Macrophages/metabolism ; Mesoderm/cytology ; Mesoderm/metabolism ; Proteomics ; Single Molecule Imaging ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Transcriptome
مستخلص: The mouse small intestine shows profound variability in gene expression along the crypt-villus axis 1,2 . Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
References: Moor, A. E., Harnik, Y., Ben-Moshe, S., Massasa, E. E., Rozenberg, M., Eilam, R., Bahar Halpern, K. & Itzkovitz, S. Spatial reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell 175, 1156–1167.e15 (2018).
Beumer, J. & Clevers, H. Cell fate specification and differentiation in the adult mammalian intestine. Nat. Rev. Mol. Cell Biol. 22, 39–53 (2021). (PMID: 32958874)
Bonis, V., Rossell, C. & Gehart, H. The intestinal epithelium—fluid fate and rigid structure from crypt bottom to villus tip. Front. Cell Dev. Biol. 9, 661931 (2021). (PMID: 340951278172987)
Manco, R. et al. Clump sequencing exposes the spatial expression programs of intestinal secretory cells. Nat. Commun. 12, 3074 (2021). (PMID: 340313738144370)
Bahar Halpern, K. et al. Lgr5+ telocytes are a signaling source at the intestinal villus tip. Nat. Commun. 11, 1936 (2020). (PMID: 323219137176679)
Shoshkes-Carmel, M. et al. Subepithelial telocytes are an important source of Wnts that supports intestinal crypts. Nature 557, 242–246 (2018). (PMID: 297206495966331)
McCarthy, N. et al. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell 26, 391–402 (2020). (PMID: 320843897412576)
Valenta, T. et al. Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Rep. 15, 911–918 (2016). (PMID: 27117411)
Sullivan, Z. A. et al. γδ T cells regulate the intestinal response to nutrient sensing. Science 371, eaba8310 (2021). (PMID: 33737460)
Bujko, A. et al. Transcriptional and functional profiling defines human small intestinal macrophage subsets. J. Exp. Med. 215, 441–458 (2017). (PMID: 29273642)
Brandtzaeg, P. et al. The B-cell system of human mucosae and exocrine glands. Immunol. Rev. 171, 45–87 (1999). (PMID: 105821657159139)
Beumer, J. et al. BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states. Cell Rep. 38, 110438 (2022). (PMID: 35235783)
Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021). (PMID: 344973898426186)
Burclaff, J. et al. A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics. Cell. Mol. Gastroenterol. Hepatol. https://doi.org/10.1016/j.jcmgh.2022.02.007 (2022).
Holloway, E. M. et al. Mapping development of the human intestinal niche at single-cell resolution. Cell Stem Cell 28, 568–580 (2021). (PMID: 33278341)
Egozi, A. et al. Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis. PLoS Biol. 21, e3002124 (2023). (PMID: 3720571110234541)
Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810–826 (2021). (PMID: 334064097864098)
Hickey, J. W. et al. Organization of the human intestine at single-cell resolution. Nature 619, 572–584 (2023). (PMID: 3746858610356619)
Zilbauer, M. et al. A Roadmap for the Human Gut Cell Atlas. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-023-00784-1 (2023).
Forrest, A. R. R. et al. A promoter-level mammalian expression atlas. Nature 507, 462–470 (2014). (PMID: 24670764)
Bausch-Fluck, D. et al. The in silico human surfaceome. Proc. Natl Acad. Sci. USA 115, E10988–E10997 (2018). (PMID: 303738286243280)
Ashburner, M. et al. Gene Ontology: tool for the unification of biology. Nat. Genet. 25, 25–29 (2000). (PMID: 108026513037419)
Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27–30 (2000). (PMID: 10592173102409)
Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417–425 (2015). (PMID: 267710214707969)
Tuganbaev, T. et al. Diet diurnally regulates small intestinal microbiome-epithelial-immune homeostasis and enteritis. Cell 182, 1441–1459 (2020). (PMID: 32888430)
Harnik, Y. et al. Spatial discordances between mRNAs and proteins in the intestinal epithelium. Nat. Metab. 3, 1680–1693 (2021). (PMID: 34931081)
Kelly, J., Weir, D. G. & Feighery, C. Differential expression of HLA-D gene products in the normal and coeliac small bowel. Tissue Antigens 31, 151–160 (1988). (PMID: 3376099)
Scott, H., Solheim, B. G., Brandtzaeg, P. & Thorsby, E. HLA-DR-like antigens in the epithelium of the human small intestine. Scand. J. Immunol. 12, 77–82 (1980). (PMID: 6997989)
Mansbach, C. M. & Siddiqi, S. A. The biogenesis of chylomicrons. Annu. Rev. Physiol. 72, 315 (2010). (PMID: 201486784861230)
Mahmood Hussain, M. A proposed model for the assembly of chylomicrons. Atherosclerosis 148, 1–15 (2000).
Chung, J. et al. LDAF1 and seipin form a lipid droplet assembly complex. Dev. Cell 51, 551–563 (2019). (PMID: 317084327235935)
Hung, Y.-H., Carreiro, A. L. & Buhman, K. K. Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat. Biochim. Biophys. Acta 1862, 600–614 (2017). (PMID: 5503214)
Barker, H. G., Malm, J. R. & Reemtsma, K. Comparative fat and fatty acid intestinal absorption test utilizing radioiodine labeling; results in normal subjects. Proc. Soc. Exp. Biol. Med. 92, 471–474 (1956). (PMID: 13359437)
Lawen, A. & Lane, D. J. R. Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid. Redox Signal. 18, 2473–2507 (2013). (PMID: 23199217)
Moor, A. E. et al. Global mRNA polarization regulates translation efficiency in the intestinal epithelium. Science 357, 1299–1303 (2017). (PMID: 287980455955215)
Zwick, R. K. et al. Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains. Nat. Cell Biol. https://doi.org/10.1038/s41556-023-01337-z (2024).
Meran, L., Baulies, A. & Li, V. S. W. Intestinal stem cell niche: the extracellular matrix and cellular components. Stem Cells Int. 2017, e7970385 (2017).
Palikuqi, B. et al. Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury. Cell Stem Cell 29, 1262–1272 (2022). (PMID: 359310349387209)
Niec, R. E. et al. Lymphatics act as a signaling hub to regulate intestinal stem cell activity. Cell Stem Cell 29, 1067–1082 (2022). (PMID: 357285959271639)
Bernier-Latmani, J. et al. ADAMTS18 + villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels. Nat. Commun. 13, 3983 (2022). (PMID: 358101689271081)
Santaolalla, R., Fukata, M. & Abreu, M. T. Innate immunity in the small intestine. Curr. Opin. Gastroenterol. 27, 125–131 (2011). (PMID: 212486353502877)
Moghaddami, M., Cummins, A. & Mayrhofer, G. Lymphocyte-filled villi: comparison with other lymphoid aggregations in the mucosa of the human small intestine. Gastroenterology 115, 1414–1425 (1998). (PMID: 9834269)
Crosnier, C., Stamataki, D. & Lewis, J. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat. Rev. Genet. 7, 349–359 (2006). (PMID: 16619050)
Brügger, M. D. & Basler, K. The diverse nature of intestinal fibroblasts in development, homeostasis, and disease. Trends Cell Biol. 33, 834–849 (2023). (PMID: 37080817)
Chiquet-Ehrismann, R. Tenascins. Int. J. Biochem. Cell Biol. 36, 986–990 (2004). (PMID: 15094113)
Treuting, P. M., Arends, M. J. & Dintzis, S. M. in Comparative Anatomy and Histology (Second Edition) (eds. Treuting, P. M. et al.) Ch. 11, 191–211 (Academic, 2018). https://doi.org/10.1016/B978-0-12-802900-8.00011-7 .
Subiran Adrados, C., Yu, Q., Bolaños Castro, L. A., Rodriguez Cabrera, L. A. & Yun, M. H. Salamander-Eci: an optical clearing protocol for the three-dimensional exploration of regeneration. Dev. Dyn. 250, 902–915 (2021). (PMID: 33084146)
Halpern, K. B. et al. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 542, 352–356 (2017). (PMID: 281665385321580)
Ben-Moshe, S. & Itzkovitz, S. Spatial heterogeneity in the mammalian liver. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-019-0134-x (2019).
Trautmann, A. Extracellular ATP in the immune system: more than just a ‘danger signal’. Sci. Signal. 2, pe6 (2009). (PMID: 19193605)
Mabley, J. G. et al. Inosine reduces inflammation and improves survival in a murine model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G138–G144 (2003). (PMID: 12388199)
Liu, T. et al. ADAMDEC1 promotes skin inflammation in rosacea via modulating the polarization of M1 macrophages. Biochem. Biophys. Res. Commun. 521, 64–71 (2020). (PMID: 31627897)
O’Shea, N. R. et al. Critical role of the disintegrin metalloprotease ADAM-like decysin-1 [ADAMDEC1] for intestinal immunity and inflammation. J. Crohns Colitis 10, 1417–1427 (2016). (PMID: 272264165174729)
Matsumoto, T. et al. Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation. Gut 50, 402–404 (2002). (PMID: 118397221773125)
Snover, D. C. Update on the serrated pathway to colorectal carcinoma. Hum. Pathol. 42, 1–10 (2011). (PMID: 20869746)
Rubio, C. A. Serrated adenoma of the duodenum. J. Clin. Pathol. 57, 1219–1221 (2004). (PMID: 155096891770477)
Lyubimova, A. et al. Single-molecule mRNA detection and counting in mammalian tissue. Nat. Protoc. 8, 1743–1758 (2013). (PMID: 23949380)
Preibisch, S., Saalfeld, S. & Tomancak, P. Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics 25, 1463–1465 (2009). (PMID: 193463242682522)
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012). (PMID: 22743772)
Bagnoli, J. W. et al. Sensitive and powerful single-cell RNA sequencing using mcSCRB-seq. Nat. Commun. 9, 2937 (2018). (PMID: 300501126062574)
Kohen, R. et al. UTAP: User-friendly Transcriptome Analysis Pipeline. BMC Bioinform. 20, 154 (2019).
Elinger, D., Gabashvili, A. & Levin, Y. Suspension trapping (S-Trap) is compatible with typical protein extraction buffers and detergents for bottom-up proteomics. J. Proteome Res. 18, 1441–1445 (2019). (PMID: 30761899)
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008). (PMID: 19029910)
Gu, Z. Complex heatmap visualization. iMeta 1, e43 (2022). (PMID: 3886871510989952)
Gu, Z., Gu, L., Eils, R., Schlesner, M. & Brors, B. circlize Implements and enhances circular visualization in R. Bioinform. Oxf. Engl. 30, 2811–2812 (2014).
Ni, Z. et al. SpotClean adjusts for spot swapping in spatial transcriptomics data. Nat. Commun. 13, 2971 (2022). (PMID: 356241129142522)
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021). (PMID: 340621198238499)
Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017). (PMID: 292038795715110)
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289–300 (1995).
Cunningham, F. et al. Ensembl 2022. Nucleic Acids Res. 50, D988–D995 (2022). (PMID: 34791404)
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005). (PMID: 161995171239896)
Caliński, T. & Harabasz, J. A dendrite method for cluster analysis. Commun. Stat. 3, 1–27 (1974).
Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021). (PMID: 33318659)
Pachitariu, M. & Stringer, C. Cellpose 2.0: how to train your own model. Nat. Methods 19, 1634–1641 (2022). (PMID: 363448329718665)
Hickey, J. W., Tan, Y., Nolan, G. P. & Goltsev, Y. Strategies for accurate cell type identification in CODEX multiplexed imaging data. Front. Immunol. 12, 727626 (2021). (PMID: 344842378415085)
Levine, J. H. et al. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162, 184–197 (2015). (PMID: 260952514508757)
Ramilowski, J. A. et al. A draft network of ligand-receptor-mediated multicellular signalling in human. Nat. Commun. 6, 7866 (2015). (PMID: 26198319)
Shannon, C. E. The mathematical theory of communication. 1963. MD Comput. 14, 306–317 (1997). (PMID: 9230594)
Harnik, Y. et al. Spatial transcriptomics data for ‘A spatial expression atlas of the adult human proximal small intestine’. Zenodo https://doi.org/10.5281/zenodo.10715015 (2024).
Harnik, Y. et al. Human villus zonation segmental tables for ‘A spatial expression atlas of the adult human proximal small intestine’. Zenodo https://doi.org/10.5281/zenodo.11490477 (2024).
Harnik, Y. et al. LCM RNA-seq and proteomics raw data for ‘A spatial expression atlas of the adult human proximal small intestine’. Zenodo https://doi.org/10.5281/zenodo.10715015 (2024).
Harnik, Y. et al. CODEX data for ‘A spatial expression atlas of the adult human proximal small intestine’. Zenodo https://doi.org/10.5281/zenodo.10724499 (2024).
Uhlén, M. et al. Tissue-based map of the human proteome. Science 347, 1260419 (2015). (PMID: 25613900)
Wang, Y. et al. Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides. Nat. Commun. 14, 5093 (2023). (PMID: 3760791210444805)
Hortsch, M. The Michigan Histology website as an example of a free anatomical resource serving learners and educators worldwide. Anat. Sci. Educ. 16, 363–371 (2023). (PMID: 36453096)
المشرفين على المادة: 0 (Chylomicrons)
E1UOL152H7 (Iron)
تواريخ الأحداث: Date Created: 20240807 Date Completed: 20240829 Latest Revision: 20240917
رمز التحديث: 20240918
DOI: 10.1038/s41586-024-07793-3
PMID: 39112711
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-024-07793-3