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Using intersection analysis of PCD\u2010 and mitochondria\u2010related genes, we identified candidate hub genes through protein\u2010protein interaction and random forest analysis. At the single\u2010cell level, key cell types were further validated based on the expression of hub genes. Additionally, we explored the transcription factors (TFs) regulating hub gene expression and the cellular heterogeneity of DFU. Finally, the expression of key hub genes and TFs was validated in clinical specimens. Our results identified BCL2 and LIPT1 as significantly downregulated hub genes in DFU, with Keratinocytes, as the key cell type. Immunohistochemistry confirmed downregulation of BCL2 and LIPT1 in DFU samples (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Additionally, TFs CEBPD and IRF1 were significantly upregulated in DFU, as confirmed by real\u2010time polymerase chain reaction analysis (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>","DOI":"10.1111\/jcmm.70319","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T04:00:26Z","timestamp":1735358426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bulk and Single\u2010Cell Transcriptome Analyses Unravel Gene Signatures of Mitochondria\u2010Associated Programmed Cell Death in Diabetic Foot Ulcer"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-4652","authenticated-orcid":false,"given":"Wenqiang","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui P. R. 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