{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:55:53Z","timestamp":1785941753460,"version":"3.56.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Advances in Wound Care"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>In a complex environment such as that in a diabetic foot ulcer (DFU), multiple factors, including cross talk between distinct cell types of the affected tissue, play a significant role. We identified a transcription factor (TF) cocktail that induces a transition from nonhealing to healing states across multiple cell types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach:<\/jats:title>\n                    <jats:p>Thirty-three skin and wound single\u2010cell RNA\u2010sequencing samples (85,928 cells) from patients with diabetes with healing or nonhealing DFU were analyzed (GSE165816). The relative activity of cell type-specific TF in healing versus nonhealing DFU was compared, and the cumulative additive effect of different TF cocktails was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We used a cumulative additive-effect approach to identify five transcription factors, FOS Like 2, AP-1 Transcription Factor Subunit (\n                      <jats:italic toggle=\"yes\">FOSL2)<\/jats:italic>\n                      , CAMP Responsive Element Binding Protein 3 Like 1, RELB Proto-Oncogene, NF-KB Subunit, ETS Proto-Oncogene 1 (\n                      <jats:italic toggle=\"yes\">ETS1<\/jats:italic>\n                      ), and X-Box Binding Protein 1, whose targets include 66.5% of pro-healing genes and only 12.5% of anti-healing genes across all cell types. In vascular endothelial cells, this TF panel accounted for 95% of vasculature-development genes; in myeloid cells, it regulated 85% of antimicrobial-response genes.\n                      <jats:italic toggle=\"yes\">In silico<\/jats:italic>\n                      knockout of\n                      <jats:italic toggle=\"yes\">ETS1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">FOSL2<\/jats:italic>\n                      shifted cells toward nonhealing states, whereas Nuclear Receptor Subfamily 3 Group C Member 1 knockout shifted endothelial cells, fibroblasts, and myeloid cells toward healing-associated state.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This work recognizes a TF panel that is likely to have therapeutic value in promoting healing in nonhealing DFU.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In this work, we identified a set of candidate TFs with the potential to induce a cell state transition favoring a switch from nonhealing to healing outcomes in patients with nonhealing DFU. Overall, our gene regulatory network-driven TF cocktail provides a rational blueprint for reprogramming DFU cell states and paves the way toward targeted regenerative therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/21621918251376348","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T22:20:26Z","timestamp":1759270826000},"page":"139-156","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Skin Multicellular Reprogramming Factors as Potential Treatment for Nonhealing Diabetic Foot Ulcers"],"prefix":"10.1177","volume":"15","author":[{"given":"Ahmed S.","family":"Abouhashem","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Graduate Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."},{"name":"Sharkia Clinical Research Department, Ministry of Health and Population, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine K.","family":"Saber","sequence":"additional","affiliation":[{"name":"Graduate Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."},{"name":"Systems Genomics Lab, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Abouzekry","sequence":"additional","affiliation":[{"name":"Graduate Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Elkholy","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Graduate Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."},{"name":"Systems Genomics Lab, The American University in Cairo, New Cairo, Egypt."},{"name":"Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0486-348X","authenticated-orcid":false,"given":"Ahmed","family":"Abdellatif","sequence":"additional","affiliation":[{"name":"Graduate Biotechnology Program, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."},{"name":"Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-0123","authenticated-orcid":false,"given":"Hassan M.E.","family":"Azzazy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Elbaz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4126-9618","authenticated-orcid":false,"given":"Kanhaiya","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 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