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Single-cell transcriptomic analysis for the identification and validation of key genes associated with metabolic cell death in pressure ulcers.

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Τίτλος: Single-cell transcriptomic analysis for the identification and validation of key genes associated with metabolic cell death in pressure ulcers.
Συγγραφείς: Dong J; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 724401006@qq.com., Ning Y; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: N15735010056@163.com., Lu C; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 17200588255@163.com., Wu W; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 449306686@qq.com., Zhang K; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 929930245@qq.com., Chai H; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 644946472@qq.com., Dong H; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 3998098874@qq.com., Sun J; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, China. Electronic address: sunjian@sxmu.edu.cn.
Πηγή: Tissue & cell [Tissue Cell] 2026 Oct; Vol. 102, pp. 103643. Date of Electronic Publication: 2026 May 28.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Churchill Livingstone Country of Publication: Scotland NLM ID: 0214745 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3072 (Electronic) Linking ISSN: 00408166 NLM ISO Abbreviation: Tissue Cell Subsets: MEDLINE
Imprint Name(s): Publication: Edinburgh : Churchill Livingstone
Original Publication: Edinburgh, Oliver & Boyd.
Ιατρικοί όροι (MeSH): Pressure Ulcer*/genetics , Pressure Ulcer*/pathology , Pressure Ulcer*/metabolism , Cell Death*/genetics , Transcriptome*/genetics , Single-Cell Analysis* , Gene Expression Profiling*, Protein Interaction Maps/genetics ; Single-Cell Gene Expression Analysis ; Humans ; Gene Regulatory Networks ; Gene Expression Regulation
Περίληψη: Background: Pressure ulcer (PU) result from sustained pressure and friction that damage the skin and underlying subcutaneous tissues. Although ferroptosis-related proteins are differentially expressed between PUs and normal skin, the role of metabolic cell death (MCD)-related genes in PUs remains unclear. In this study, we aimed to identify MCD-related genes (MCD-RGs) associated with PUs using single-cell transcriptomic analysis and to explore their potential mechanisms.
Methods: Differentially expressed genes were identified in key cell clusters from the PU single-cell dataset GSE137897 and intersected with MCD-RGs to obtain candidate genes. Key genes were screened through protein-protein interaction (PPI) network analysis, followed by regulatory network construction, drug prediction, enrichment analysis, pseudotime analysis, and validation using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: Key cells included immune cell clusters 1 and 2 and melanocytes. A total of 78 candidate genes and eight key genes were identified. These genes were predicted to be regulated by 40 transcription factors (TFs), to be associated with relevant biological pathways, and to be linked to 58 potential compounds. JUN differed significantly across all key cells, whereas ACTB showed stable changes. RT-qPCR results showed that ACTB, IKBKB, and JUN were upregulated in PUs.
Conclusion: The integration of eight key genes identified through single-cell transcriptomic analysis provides new insights into the molecular mechanisms of PU and may help identify potential therapeutic targets.
(Copyright © 2026 Elsevier Ltd. All rights reserved.)
Competing Interests: Declaration of competing Interests The authors declare no competing interests.
Contributed Indexing: Keywords: Cell death; Drug discovery; Gene expression regulation; Pressure ulcer; Single-cell analysis
Entry Date(s): Date Created: 20260531 Date Completed: 20260716 Latest Revision: 20260716
Update Code: 20260717
DOI: 10.1016/j.tice.2026.103643
PMID: 42218835
Βάση Δεδομένων: MEDLINE
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  Label: Title
  Group: Ti
  Data: Single-cell transcriptomic analysis for the identification and validation of key genes associated with metabolic cell death in pressure ulcers.
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  Data: <searchLink fieldCode="AU" term="%22Dong+J%22">Dong J</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 724401006@qq.com.<br /><searchLink fieldCode="AU" term="%22Ning+Y%22">Ning Y</searchLink>; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: N15735010056@163.com.<br /><searchLink fieldCode="AU" term="%22Lu+C%22">Lu C</searchLink>; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 17200588255@163.com.<br /><searchLink fieldCode="AU" term="%22Wu+W%22">Wu W</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 449306686@qq.com.<br /><searchLink fieldCode="AU" term="%22Zhang+K%22">Zhang K</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 929930245@qq.com.<br /><searchLink fieldCode="AU" term="%22Chai+H%22">Chai H</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 644946472@qq.com.<br /><searchLink fieldCode="AU" term="%22Dong+H%22">Dong H</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: 3998098874@qq.com.<br /><searchLink fieldCode="AU" term="%22Sun+J%22">Sun J</searchLink>; Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, China. Electronic address: sunjian@sxmu.edu.cn.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Churchill+Livingstone%22">Churchill Livingstone </searchLink><i>Country of Publication: </i>Scotland <i>NLM ID: </i>0214745 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1532-3072 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200408166%22">00408166 </searchLink><i>NLM ISO Abbreviation: </i>Tissue Cell <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Edinburgh : Churchill Livingstone<br /><i>Original Publication</i>: Edinburgh, Oliver & Boyd.
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  Data: <searchLink fieldCode="MM" term="%22Pressure+Ulcer%22">Pressure Ulcer*</searchLink>/<searchLink fieldCode="MM" term="%22Pressure+Ulcer+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Pressure+Ulcer%22">Pressure Ulcer*</searchLink>/<searchLink fieldCode="MM" term="%22Pressure+Ulcer+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Pressure+Ulcer%22">Pressure Ulcer*</searchLink>/<searchLink fieldCode="MM" term="%22Pressure+Ulcer+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Cell+Death%22">Cell Death*</searchLink>/<searchLink fieldCode="MM" term="%22Cell+Death+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcriptome%22">Transcriptome*</searchLink>/<searchLink fieldCode="MM" term="%22Transcriptome+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Single-Cell+Analysis%22">Single-Cell Analysis*</searchLink> <br /><searchLink fieldCode="MM" term="%22Gene+Expression+Profiling%22">Gene Expression Profiling*</searchLink><br /><searchLink fieldCode="MH" term="%22Protein+Interaction+Maps%22">Protein Interaction Maps</searchLink>/<searchLink fieldCode="MH" term="%22Protein+Interaction+Maps+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Single-Cell+Gene+Expression+Analysis%22">Single-Cell Gene Expression Analysis</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Regulatory+Networks%22">Gene Regulatory Networks</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%22">Gene Expression Regulation</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Pressure ulcer (PU) result from sustained pressure and friction that damage the skin and underlying subcutaneous tissues. Although ferroptosis-related proteins are differentially expressed between PUs and normal skin, the role of metabolic cell death (MCD)-related genes in PUs remains unclear. In this study, we aimed to identify MCD-related genes (MCD-RGs) associated with PUs using single-cell transcriptomic analysis and to explore their potential mechanisms.<br />Methods: Differentially expressed genes were identified in key cell clusters from the PU single-cell dataset GSE137897 and intersected with MCD-RGs to obtain candidate genes. Key genes were screened through protein-protein interaction (PPI) network analysis, followed by regulatory network construction, drug prediction, enrichment analysis, pseudotime analysis, and validation using reverse transcription quantitative polymerase chain reaction (RT-qPCR).<br />Results: Key cells included immune cell clusters 1 and 2 and melanocytes. A total of 78 candidate genes and eight key genes were identified. These genes were predicted to be regulated by 40 transcription factors (TFs), to be associated with relevant biological pathways, and to be linked to 58 potential compounds. JUN differed significantly across all key cells, whereas ACTB showed stable changes. RT-qPCR results showed that ACTB, IKBKB, and JUN were upregulated in PUs.<br />Conclusion: The integration of eight key genes identified through single-cell transcriptomic analysis provides new insights into the molecular mechanisms of PU and may help identify potential therapeutic targets.<br /> (Copyright © 2026 Elsevier Ltd. All rights reserved.)
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  Data: Declaration of competing Interests The authors declare no competing interests.
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  Data: <i>Keywords: </i>Cell death; Drug discovery; Gene expression regulation; Pressure ulcer; Single-cell analysis
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        Value: 10.1016/j.tice.2026.103643
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        Text: English
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        StartPage: 103643
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      – SubjectFull: Protein Interaction Maps genetics
        Type: general
      – SubjectFull: Single-Cell Gene Expression Analysis
        Type: general
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      – SubjectFull: Pressure Ulcer metabolism
        Type: general
      – SubjectFull: Cell Death genetics
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              Text: 2026 Oct
              Type: published
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