{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:02:08Z","timestamp":1789671728232,"version":"4.0.1"},"reference-count":108,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6817","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,9,17]]},"abstract":"<jats:p>Cell-state diversity drives tissue adaptability, repair, and disease resilience, but capturing this complexity is a challenge. Current approaches rely on transcriptional profiling and overlook organelle structure, a key indicator of metabolism and stress. We developed spatial Organellomics (sOrganellomics), an imaging workflow that integrates automated segmentation with machine learning to classify and spatially map cell states from multi-organelle signatures. In liver and pancreas, these signatures distinguished broad cellular classes. In liver, sOrganellomics revealed that zonal position did not fully explain organelle-defined hepatocyte categories. Instead, hepatocytes formed intermixed communities within canonical zones, supporting a refined subzonal diversity model. Nutritional stress reshaped this organization. Intravital imaging linked fasting-induced organelle remodeling with altered mitochondrial membrane potential in vivo, supporting multi-organelle architecture as a structural readout of tissue adaptation.<\/jats:p>","DOI":"10.1126\/science.ady6372","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:02:51Z","timestamp":1789668171000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Multi-organelle signatures map cell-state diversity and metabolic adaptation in tissues"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8561-4456","authenticated-orcid":true,"given":"Raghabendra","family":"Adhikari","sequence":"first","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-2104","authenticated-orcid":true,"given":"Alexander","family":"Hillsley","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."},{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8325-5470","authenticated-orcid":true,"given":"Alana Dowdell","family":"Johnson","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."},{"name":"Janelia-Meyerhoff Undergraduate Scholars Program 2024."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-8348","authenticated-orcid":true,"given":"Shihong Max","family":"Gao","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0510-527X","authenticated-orcid":true,"given":"Isabel","family":"Espinosa-Medina","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-7783","authenticated-orcid":true,"given":"Jan","family":"Funke","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-4006","authenticated-orcid":true,"given":"Daniel","family":"Feliciano","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081751"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.016"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02119-z"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201900221"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01033-y"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01182-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0318-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.11.018"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.07.008"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00963-z"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210777"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2012.06.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00042"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","unstructured":"S. Sengupta D. L. Levy \u201cOrganelle Communication with the Nucleus\u201d in Intercellular and Interorganellar Transfer and Communication in Biology and Medicine M. Kloc J. Z. Kubiak M. Halasa Eds. (Springer International 2024 vol. 73 of Results and Problems in Cell Differentiation pp. 3\u201323.","DOI":"10.1007\/978-3-031-62036-2_1"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13820"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01788-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8872639"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04488-5"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48272-7"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01547-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12083"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00845-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2021.148393"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00026.2019"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01136-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E24-06-0252"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45751-9"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.13"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-11-71"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3700"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39811-9"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116280"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","unstructured":"S. Krispin W. Van Zuiden Y. M. Danino L. Molitor N. Rudberg C. Bar A. Coyne T. Meimoun F. M. Waldron J. M. Gregory T. Fisher A. Nachshon N. Stern-Ginossar N. Yacovzada E. Hornstein Organellomics: AI-driven deep organellar phenotyping reveals novel ALS mechanisms in human neurons. bioRxiv 10.1101\/2024.01.31.572110 [Preprint] (2024); https:\/\/doi.org\/10.1101\/2024.01.31.572110.","DOI":"10.1101\/2024.01.31.572110"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02528-8"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118800"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2024.102345"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01663-4"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.002"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14176-0"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112435"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00783-1"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00962-0"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.03.015"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.08.012"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-8165(76)80083-2"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(92)90055-5"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.16.070196.001143"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031521-024831"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0134-x"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46206"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0109-9"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21065"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11634-020-00393-9"},{"key":"e_1_3_2_55_2","first-page":"1","article-title":"Bayesian Sparse Gaussian Mixture Model for Clustering in High Dimensions","volume":"26","author":"Yao D.","year":"2025","unstructured":"D. Yao, F. Xie, Y. Xu, Bayesian Sparse Gaussian Mixture Model for Clustering in High Dimensions. J. Mach. Learn. Res. 26, 1\u201350 (2025). 41799364","journal-title":"J. Mach. Learn. Res."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1080\/10618600.2019.1647846"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00357-021-09409-1"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01316-4"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02007-6"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01358-2"},{"key":"e_1_3_2_61_2","unstructured":"R. O. Duda P. E. Hart D. G. Stork Pattern Classification (Wiley New York ed. 2. 2001)."},{"key":"e_1_3_2_62_2","volume-title":"Elements of Information Theory","author":"Cover T. M.","year":"2006","unstructured":"T. M. Cover, J. A. Thomas, Elements of Information Theory (Wiley-Interscience, ed. 2, 2006).","edition":"2"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102678"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.10.007"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.002"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01104-w"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116025"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00025.2010"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.466656"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0256-9"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.09.002"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07713-9"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77214-0"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2309-1_22"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091308"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69413"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008462"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011582"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314762"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.65044"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12020397"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1373-2"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103233"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq2084"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.05.022"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201500124"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130024"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100754"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44860"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-53309-4"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00205.2023"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adv7129"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0258-4"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.014"},{"key":"e_1_3_2_95_2","unstructured":"R. Adhikari A. Hillsley A. Dowdell Johnson I. Espinosa Medina J. Funke D. Feliciano Raw images for: \u201cSpatial Organellomics Maps Cell State Diversity and Metabolic Adaptation in Tissues \u201d Janelia Research Campus (2026); https:\/\/doi.org\/10.25378\/JANELIA.31863250."},{"key":"e_1_3_2_96_2","unstructured":"R. Adhikari A. Hillsley A. Dowdell Johnson I. Espinosa Medina J. Funke D. Feliciano Spatial Organellomics tissue- cell- and organelle-level dataset from mouse liver. Janelia Research Campus (2026); https:\/\/doi.org\/10.25378\/JANELIA.32717316."},{"key":"e_1_3_2_97_2","unstructured":"A. Hillsley R. Adhikari D. Feliciano D. Adjavon M. Aronson liv_zones: Spatial organelle segmentation and mapping pipeline for fluorescence microscopy version 1.0.0 Zenodo (2026); https:\/\/doi.org\/10.5281\/ZENODO.21808753."},{"key":"e_1_3_2_98_2","unstructured":"D. Feliciano R. Adhikari A. Hillsley Spatial-Organellomics: manuscript analysis code version v1.0.0 Zenodo (2026); https:\/\/doi.org\/10.5281\/ZENODO.21810468."},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-025-02624-3"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01336-8"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00748-9"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.patcog.2012.07.021"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10489-022-03939-w"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-71050-9"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1561\/2200000073"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1002\/nav.3800020109"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1214\/088342304000000396"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1538-7305.1948.tb01338.x"},{"key":"e_1_3_2_109_2","unstructured":"B. Efron R. Tibshirani An Introduction to the Bootstrap (Chapman & Hall Boca Raton Fla. Nachdr. 1998)Monographs on statistics and applied probability."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.ady6372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:03:44Z","timestamp":1789668224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.ady6372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":108,"journal-issue":{"issue":"6817","published-print":{"date-parts":[[2026,9,17]]}},"alternative-id":["10.1126\/science.ady6372"],"URL":"https:\/\/doi.org\/10.1126\/science.ady6372","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"2025-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eady6372"}}