Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and...

Area of Science:

• Single-cell transcriptomics
• Cell biology
• Stem cell research

Background:

• Mesenchymal stromal cells (MSCs) and fibroblasts share similar characteristics, leading to blurred identities and limited applications.
• Distinguishing between MSCs and fibroblasts is crucial for their effective use in research and therapy.

Purpose of the Study:

• To investigate the heterogeneity of human MSCs (HuMSCs, FSMSCs, BMSCs, ADMSCs) and fibroblasts using single-cell transcriptome sequencing.
• To clarify the relationship between MSCs and fibroblasts by analyzing their distinct cell subsets and molecular profiles.

Main Methods:

• Performed single-cell transcriptome sequencing on HuMSCs and FSMSCs, and integrated public data from BMSCs and ADMSCs.
• Conducted quality control, batch correction, integration, and clustering analysis of the combined dataset.
• Annotated cell subsets based on established surface marker phenotypes for MSCs, fibroblasts, and pericytes, and analyzed fibroblast marker expression.

Main Results:

• Identified 15 distinct cell subsets, with 12 showing MSC phenotype, 2 showing both MSC and pericyte phenotypes, and all 15 showing fibroblast phenotype.
• Exclusive fibroblast subsets (C8, C12, C13) were less primitive and more differentiated.
• Discovered 3,275 differentially expressed genes, 305 enriched gene sets, and 34 enriched regulons distinguishing the cell subsets.

Conclusions:

• MSCs represent a subclass of fibroblasts, as MSC phenotype subsets also exhibited fibroblast markers, but not vice versa.
• MSCs and fibroblasts are highly heterogeneous populations comprising distinct subsets.
• Differentially enriched gene sets and regulons can identify these subsets, defining their specific proliferating, differentiating, metabolic, and immunomodulatory functions.