Abstract
BackgroundAdipose-derived mesenchymal stem cells (AD-MSCs) are a type of stem cell that is abundant and widely used. The molecular characteristics of AD-MSCs from different passages from donors of different ages have not been well elucidated.MethodsSix kinds of AD-MSCs ((E1, E2, E3, Y1, Y2, and Y3) with E denoting cells derived from an elderly patient, Y denoting cells derived from a young patient, and 1, 2, and 3 representing passages 3, 6, and 10) were obtained from human abdominal adipose tissue. We obtained the protein expression profile, the mRNA expression profile, the lncRNA expression profile, and the methylation profile of each kind of AD-MSC by sequencing. After calculating the stemness indices, genes related to stemness were extracted. The multiomics correlation analysis was performed in the stemness-related genes. In addition, short time-series expression miner (STEM) analysis was performed for all cell passages and donor ages. To further explore the biological functions of the stemness-related genes, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, the lncRNA-KEGG network and transcription factor (TF)-KEGG network were constructed based on the RNAInter database and TRRUST v2 database.ResultsThe stemness of the Y1, E1, and Y2 cells was higher than that of the E2, Y3, and E3 cells. The stemness was the highest for Y1 cells and the lowest for E3 cells. STEM analysis showed that five stemness-related gene clusters were associated with the cell passages, and only one gene cluster was associated with age. The enrichment analysis results showed that the biological processes (BPs) and KEGG pathways were mainly involved in the proliferation, differentiation, and migration of cells. The global regulatory landscape of AD-MSCs was constructed: 25 TFs and 16 lncRNAs regulated 21 KEGG pathways through 27 mRNAs. Furthermore, we obtained a core stemness-related gene set consisting of ITGAV, MAD2L1, and PCNA. These genes were expressed at higher levels in Y1 cells than in E3 cells.ConclusionThe multiomics global landscape of stemness-related gene clusters was determined for AD-MSCs, which may be helpful for selecting AD-MSCs with increased stemness.
Highlights
When used for different therapeutic procedures aimed at treating various forms of tissue damage, the autologous fat graft is a solution
The multiomics global landscape of stemness-related gene clusters was determined for Adipose-derived mesenchymal stem cells (AD-MSCs), which may be helpful for selecting AD-MSCs with increased stemness
Multiomics atlas of genes related to AD-MSC stemness A total of 19,189 messenger RNA (mRNA), 21,965 Long non-coding RNA (lncRNA), and 3205 proteins were included in these analyses
Summary
When used for different therapeutic procedures aimed at treating various forms of tissue damage, the autologous fat graft is a solution. Recent studies have shown that adipose-derived stromal vascular fractions (AD-SVFs) [1, 2] and adipose-derived stem cells (ASCs) [3, 4] can enhance tissue regeneration potential [5]. ASCs have the ability to differentiate into cells of mesenchymal origin in vitro; this includes osteoblasts, adipocytes, and chondrocytes. They can enhance different tissues in vivo, including cartilage, muscle, bone, and fat [5]. Adipose-derived human follicle stem cells (AD-HFSCs) are helpful for hair regrowth [9]. Adipose-derived mesenchymal stem cells (AD-MSCs) contribute to wound healing and soft tissue defects [8]. The molecular characteristics of AD-MSCs from different passages from donors of different ages have not been well elucidated
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