{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:51:35Z","timestamp":1792788695658,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Novo Nordisk Foundation Center for Stem Cell Medicine","award":["NNF21CC0073729"],"award-info":[{"award-number":["NNF21CC0073729"]}],"id":[{"id":"https:\/\/ror.org\/03nqjyg83","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Agence Nationale de la Recherche","award":["ANR24-CPJ1-0181-01"],"award-info":[{"award-number":["ANR24-CPJ1-0181-01"]}],"id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Research Council","award":["SPARK 101140863"],"award-info":[{"award-number":["SPARK 101140863"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Spatial metabolomics revealed persistent injured tissue niches after ischemic injury despite the presence of apparently healthy epithelial cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Proximal tubule cells residing in injured niches exhibited succinate accumulation and linoleic acid depletion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Integration with spatial transcriptomics showed that injured niches were characterized by dysregulated oxidative and lipid metabolism.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The role of the tissue microenvironment in the transition from AKI to CKD remains poorly understood. While the persistence of failed-repair proximal tubule (FR-PT) cells is postulated to hamper kidney regeneration, the spatial metabolic architecture of injured tissue and its effect on regenerative capacity have not been fully characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed mouse kidneys 14 days after bilateral ischemia-reperfusion injury using a multimodal spatial omics approach. Internal standard\u2013normalized mass spectrometry imaging was used to quantify metabolite abundances, followed by unsupervised spatial domain analysis using the BANKSY algorithm to identify tissue niches on the basis of lipidome profiles. Consecutive sections underwent high-resolution spatial transcriptomics (Stereo-seq), and we applied niche projection to integrate metabolomic and transcriptomic data, enabling comparison of proximal tubule cells in healthy versus injured niches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Unsupervised spatial domain analysis revealed distinct healthy and injured niches, with injured niches exhibiting diffusely spread metabolic abnormalities extending beyond FR-PT cells. Quantitative metabolomics demonstrated that seemingly healthy proximal tubule cells residing in injured niches exhibited elevated succinic acid and depleted linoleic acid compared with cells in healthy niches. Spatial transcriptomics confirmed these metabolic defects at the transcriptional level, revealing downregulation of oxidative phosphorylation and fatty acid\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -oxidation pathways in proximal tubule cells within injured microenvironments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Combined spatially resolved analysis of internal standard\u2013normalized mass spectrometry imaging and spatial transcriptomics revealed distinct healthy and injured tissue niches after ischemia-reperfusion injury. Metabolic abnormalities, including defects in oxidative phosphorylation and fatty acid\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -oxidation, were not restricted to FR-PT cells but extended into seemingly healthy epithelial cells embedded within injured microenvironments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001216","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:01:06Z","timestamp":1785772866000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Impaired Metabolic Remodeling Characterizes Injured Niches during Post-ischemic Kidney Repair"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-4482","authenticated-orcid":false,"given":"Rosalie G.J.","family":"Rietjens","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 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Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5913-436X","authenticated-orcid":false,"given":"Wendy M.P.J.","family":"Sol","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-2149","authenticated-orcid":false,"given":"Ahmed","family":"Mahfouz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-1894","authenticated-orcid":false,"given":"Martin","family":"Giera","sequence":"additional","affiliation":[{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5726-5777","authenticated-orcid":false,"given":"Bernard M.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9958-3485","authenticated-orcid":false,"given":"S\u00e9bastien J.","family":"Dumas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Metabolic and Cardiovascular Diseases, University of Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-8892","authenticated-orcid":false,"given":"Gangqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Children's Hospital of Fudan University, and The Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-5186","authenticated-orcid":false,"given":"Ton J.","family":"Rabelink","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, The 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