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A key driver of this dysfunction is the loss of \u03b2-cell identity, which reduces functional \u03b2-cell mass and leads to inadequate insulin secretion. Periodontal pathogens have been implicated in promoting insulin resistance; however, their role in the transformation of \u03b2-cell identity remains poorly understood. This study aims to investigate the impact of periodontal pathogen\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      (\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      ) on \u03b2-cell identity maintenance and the underlying molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing (scRNA-seq) data from human pancreatic islets of nondiabetic (ND), prediabetic (Pre-T2D), and type 2 diabetes (T2D) donors were analyzed to assess changes in \u03b2-cell proportion, differentiation trajectory, and associated molecular pathways. The Single-cell Analysis of Host-Microbiome Interactions (SAHMI) method was used to detect\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      sequences in pancreatic islets. Pearson correlation analysis identified key genes associated with the action of\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      , followed by in vitro validation using a co-culture model of\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      and MIN6 cells to elucidate the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA-seq analysis revealed a reduced proportion of \u03b2-cells and decreased expression of key \u03b2-cell identity-maintenance genes in the T2D group. The expression levels of transdifferentiation markers and \u03b2-cell disallowed genes were elevated, alongside a trend toward \u03b1-cell transdifferentiation. The NF-\u03baB signaling pathway was significantly activated in the T2D group, accompanied by a significant increase in the SPP1 inflammatory signal, while the WNT pathway was markedly diminished. Integrated Pearson correlation and in vitro analyses identified the cell cycle regulator CDKN1C as a central mediator through which\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      promotes \u03b2-cell identity loss. Mechanistically,\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      activated the NF-\u03baB pathway, leading to downregulation of CDKN1C expression and thereby promoting loss of \u03b2-cell identity, which played an important role in the progression of diabetes associated with periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that \u03b2-cells in T2D primarily undergo transdifferentiation towards \u03b1-cells, and the periodontal pathogen\n                      <jats:italic>F. nucleatum<\/jats:italic>\n                      promotes \u03b2-cell identity loss via NF-\u03baB-mediated downregulation of CDKN1C.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07981-x","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:06:31Z","timestamp":1773075991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell RNA-seq and in vitro study reveal Fusobacterium nucleatum impairs \u03b2-cell identity in type 2 diabetes via the NF-\u03baB\u2013CDKN1C axis"],"prefix":"10.1186","volume":"24","author":[{"given":"Ziyi","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4055-226X","authenticated-orcid":false,"given":"Qiang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"issue":"1","key":"7981_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41392-024-01951-9","volume":"9","author":"X Lu","year":"2024","unstructured":"Lu X, Xie Q, Pan X, Zhang R, Zhang X, Peng G, et al. 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