{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:48:25Z","timestamp":1793749705882,"version":"4.6.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011930","name":"Beijing Medical and Health Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR) is driven by chronic hyperglycemia and involves coordinated vascular, inflammatory, and neuroglial dysfunction. M\u00fcller glia are central to retinal homeostasis, yet their cell-state heterogeneity and inflammatory response programs in DR mice remain incompletely characterized at single-cell resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reanalyzed a public scRNA-seq dataset of STZ-induced diabetic mouse retinas to characterize retinal cell populations and M\u00fcller glial states through clustering, perturbation, trajectory, functional enrichment, and co-expression network analyses, with selected targets further validated by Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Integration and clustering of the scRNA-seq dataset identified the major retinal cell types as well as four distinct M\u00fcller glial subpopulations. Among annotated retinal cell populations, M\u00fcller glia showed the strongest transcriptional perturbation in the STZ group, indicating that they are among the most transcriptionally responsive retinal cell types under diabetic stress. Pseudotime analysis supported the presence of branch-dependent transcriptional programs among M\u00fcller subclusters and suggested that STZ conditions were associated with preferential progression toward a M\u00fcller substate enriched for photoreceptor-associated transcripts. Functional enrichment analysis showed that different M\u00fcller glial subclusters were associated with distinct biological processes, while sharing activation of inflammatory-response programs, and highlighted\n                      <jats:italic>Cebpb<\/jats:italic>\n                      as a candidate inflammation-associated factor. Co-expression network analysis further identified M\u00fcller glia-associated gene modules with subcluster- and condition-dependent activity patterns, including modules linked to photoreceptor-associated programs, stress responses, angiogenesis and inflammatory signaling. Protein-protein interaction analysis prioritized\n                      <jats:italic>Junb<\/jats:italic>\n                      as a highly connected candidate regulatory hub, and western blotting provided supportive tissue-level evidence for altered JUNB and CEBPB protein abundance in STZ versus control retinas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We delineated the transcriptional heterogeneity of M\u00fcller glia and identified candidate state-associated modules and regulators linked to diabetic retinal stress responses. These findings support an active role for M\u00fcller glia in diabetic retinal remodeling through inflammatory, structural, and neuron-interactive programs, and provide a basis for future mechanistic and translational investigation of M\u00fcller glia-mediated pathology in diabetic retinopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1827122","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:05:46Z","timestamp":1777442746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Single cell transcriptomic analysis reveals pathogenic cell heterogeneity and candidate inflammatory-associated markers in STZ-induced diabetic mouse retina"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuai","family":"Ouyang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical 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Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]},{"name":"Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences (2019RU025)","place":["Wenzhou, Zhejiang, China"]},{"name":"Beijing Key Laboratory of Fundus Diseases Intelligent Diagnosis & Drug\/Device Development and Translation","place":["Beijing, China"]},{"name":"Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences","place":["Beijing, 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