Single-cell sequencing technology in diabetic wound healing: New insights into the progenitors-based repair strategies

Table 1 The results of single-cell sequencing in diabetic wound healing

Objective	Major findings	Cell quantity	Changes at molecular level	Changes at cellular level	Signaling pathway changes	Ref.
Of 11 healthy subjects, 9 DFU healings, and 5 DFU non-healings	Some targeting genes, such as ANPEP, BID, CYBA, CYBB, FCER1G, ITGA1, and PLAUR were found in DFUs	94325	ANPEP, BID, CYBA, CYBB, FCER1G, ITGA1, PLAUR, CD19, ITGAM, and HLA-DR up-regulated in patients with DFUs	Macrophages, white blood cells, and monocytes increased in DFUs; pluripotent stem cells and stromal cells increased in DMs	-	[7]
Of 10 non-DMs and 17 DMs (11 DFUs and 6 non-DFUs)	The CCL2-ACKR1 signal pathway may be closely associated with DFU wound healing	-	CXCL11, MMP1, HS3ST2, CALML, LCK, LDLRAD2, S10OA1, and MAMDC2 up-regulated	Tissue stem cells and endothelial cells increased in DFUs	CCL, PROS, EDN, PERIOSTIN, and PARs activated in healing DFU tissues; FGF, SEMA3, MK, PIN, and TGF activated in DFUs	[8]
Of 10 non-DMs, 6 DMs, and 11 DFUs (7 healers; 4 Non-healers)	A new type of fibroblast named HE-Fibro was found in the DFUs	174962	IL7R, TCF7, CCR7, IL1B, S100A, HIF1A, TNF, STAT5a/b, TLR7, TLR9, IL17R/C, IL6, PLA2G2A, FOS, TNFAIP6, MMP1, and CHI3L1 up-regulated, while CD44, TGFβ1, CCL5, NFKBIA, SOX4, TGFβ1, and NANOG down-regulated in DFU-healers; NKG7, GNLY, CCL5, KLRD1, DAB2, CD163, TYMP, and ANXA1 up-regulated in DFU-non-healers	CCR7+, LEF1+ naive T cells, M1 macrophage, IL17+ cells, and HE-fibroblasts increased in DFU-healers; M2 macrophage increased in DFU-non-healers	IL-6, IL-8, CD28 signaling pathways, iCOS-iCOSL pathways inhibited in DFU-healers; RhoGDI, EIF2 signaling pathways; IL6, HIF1A, ILK signaling pathways activated in DFU-healers	[9]
Of 1 non-DM, 2 T2DMs	Some differentially expressed genes were found as keratinocyte-related gene, such as LUCAT1, MAL2 and MXD1	21819	ARG1, PHYH, PKLR, PHKG1, ADH4, AQP9, HADH, PC, and ARG2 up-regulated in T2DM patients	-	Oxidative phosphorylation pathway, antigen processing and presentation pathway, tight junction pathway, amyotrophic lateral sclerosis pathway, vasopressin-regulated water reabsorption pathway activated in T2DM patients	[10]
DMs, non-DMs, STZ-induced diabetic mice	RAB17 in DFU-HDMECs may be the key factor of angiogenic capacity in DFUs	-	RAB17, CD200, HIF-1α and VEGF-A down-regulated in DFU patients	-	Hallmark-KRAS-signaling-on activated in DFU HDMECs; hallmark-angiogenesis, hallmark-epithelial-mesenchymal-transition, hallmark-inflammatory-responses, and hallmark-TNFα-signaling-via-NFκB inhibited in DFU HDMECs	[11]

DM: Diabetes mellitus; T2DM: Type 2 diabetes mellitus; DFU: Diabetic foot ulcer; MMP: Matrix metalloproteinase; CXCL11: CXC chemokine ligand 11; TNFAIP6: Tumor necrosis factor-alpha-stimulated gene-6; IL: Interleukin; TGF: Transforming growth factor; HIF: Hypoxia inducible factor; TNF: Tumor necrosis factor; NFκB: Nuclear factor-kappaB.