| Background:Diabetes foot ulcers is a kind of foot infection,ulcer and(or)deep tissue destruction in diabetes patients due to nerve abnormalities and varying degrees of vascular diseases in the distal lower limbs.In clinical practice,there are manifestations of neuropathy,such as dry and sweatless skin on the affected limb,tingling,burning pain,numbness,decreased sensation or loss of sensation on the limbs,skin sock like sensation,and feeling like stepping on cotton wool during movement.There are also manifestations of lower limb ischemia,such as lack of skin nutrition,muscle atrophy,dry skin,decreased elasticity,decreased skin temperature,pigmentation,weakened or disappeared limb arterial pulsation,and may also be accompanied by intermittent claudication symptoms in the lower limbs.As the disease progresses,there may be resting pain,gangrene at the toe,ulcers at the compressed area of the heel or metatarsophalangeal joint,and some patients may experience limb infections.The above symptoms have brought unbearable pain to patients in their daily life and work,seriously affecting their quality of life.Revealing the mechanism of wound nonunion in patients with diabetes foot has been the goal of medical scholars for many years,but so far the mechanism has not been fully clarified.Single cell whole genome sequencing technology is a new technology to amplify and sequence the whole genome at the single cell level.Its principle is to amplify the micro whole genome of a single cell separated from the tissue,eliminate interference factors to obtain a complete genome with high coverage,and then conduct high-throughput sequencing to reveal the differences,evolutionary relationships and gene differences between cell populations.This technology has unique advantages in studying the pathogenesis and is increasingly being applied in clinical research.We found the data set of single cell RNA sequencing(scRNA seq)of diabetes foot by searching the GEO database.The data set includes the single cell sequencing data of non diabetes foot and diabetes foot cells,and used this data for analysis.Objective:Through single cell sequencing,we analyzed the differences between non diabetes foot and diabetes foot in terms of cell and homologous cell genes,further revealed the pathogenesis of diabetes foot cells and genes,provided theoretical support for precise treatment of diabetes foot,and provided new ideas and strategies for the treatment of diabetes foot.Method:Download the GSE165816 gene expression data set from the GEO,and select the data set related to skin cells of non diabetes foot and diabetes foot patients.Single cell analysis was carried out to identify different cell clusters in transcription from the selected cell bank,compare cell differences,and then compare and analyze the genes of the same type of cells,so as to reveal the pathogenesis of cells and genes in diabetes foot.Results:(1)Compared with non diabetes foot,the number of NK cells,plasma cells,myeloid cells and T cells in the foot skin of diabetes foot patients increased significantly,and the number of smooth muscle cells,keratinocytes and basal cells decreased significantly.(2)The feet of patients with diabetes foot gradually transform from basal cells to keratinocytes.In this process,the genes H2AF2,S100A6,FTH1,MT2A,FTL,HMGB1 and other genes in basal cells gradually decrease expression.These genes are related to wound healing,structural components of cytoskeleton,binding to RAGE receptors and other metabolic processes.The KRT14 and CXCL4 genes showed a trend of low expression high expression low expression.Genes such as LGALS7B,PERP,SFN,TACSTD2,CALML5,PKP1,CSTA,JUP in keratinocytes are gradually overexpressed,which are related to metabolic processes such as keratinization,desmosome formation,and peptide cross-linking.(3)The foot of patients with diabetes foot will gradually transform from basal cells to keratinocytes.In this process,the genes H2AF2,S100A6,FTH1,MT2A,FTL,HMGB1 in basal cells gradually decrease expression,these genes are associated with wound healing,structural constituent of cytoskeleton and other metabolic processes and the genes KRT14 and CXCL4 show a trend of low expression-high expression-low expression.Genes such as LGALS7B,PERP,SFN,TACSTD2,CALML5,PKP1,CSTA,and JUP are gradually overexpressed in keratinocytes.These genes are associated with metabolic processes such as RAGE receptor binding,formation of the comified envelope desmosome,and peptide crosslinking.(4)Compared with non diabetes foot,diabetes foot patients have significantly different genes in smooth muscle cells,basal cells,B cells,mast cell,NK cells,keratinocytes,and T cells,as well as GO and KEGG difference results.Conclusion:(1)At the cellular level,the number of NK cells,plasma cells,myeloid cells and T cells increased significantly in patients with diabetes foot,and the number of smooth muscle cells,keratinocytes and basal cells decreased significantly.The type Ⅰ,Ⅳ and VI collagen receptors of fibroblasts and smooth muscle cells in the patients with diabetes foot significantly enhanced their communication relationship with CD44 ligand in other cells,and the laminin related receptors of fibroblasts,endothelial cells and smooth muscle cells significantly enhanced their communication relationship with CD44 ligand in other cells.(2)At the gene level,the patients with diabetes foot gradually transform from basal cells to keratinocytes.In this process,the genes H2AF2,S100A6,FTH1,MT2A,FTL,and HMGB1 in basal cells gradually lower expression,and the genes KRT14 and CXCL4 show a trend of low expression-high expression-low expression.Genes such as LGALS7B,PERP,SFN,TACSTD2,CALML5,PKP1,CSTA,JUP in keratinocytes are gradually overexpressed.With the transformation from basal cells to keratinocytes,the metabolic processes such as wound healing,cytoskeleton structural components,and binding to RAGE receptors gradually decrease,while the metabolic processes such as keratinization,desmosome formation,and peptide cross-linking gradually increase. |
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