Single-cell transcriptome atlas of human mesenchymal stem cells exploring cellular heterogeneity

Area of Science:

• Stem Cell Biology
• Genomics
• Immunology

Background:

• Mesenchymal stem cell (MSC) heterogeneity hinders clinical applications and research reproducibility.
• Advanced single-cell RNA sequencing (scRNA-seq) is crucial for dissecting cellular heterogeneity.
• A comprehensive single-cell atlas for human MSCs has been lacking.

Purpose of the Study:

• To construct a comprehensive single-cell atlas of human MSCs to characterize their heterogeneity.
• To identify distinct MSC subpopulations across multiple tissues and donors.
• To understand the molecular drivers of MSC heterogeneity and their functional implications.

Main Methods:

• Massive parallel multiplexing scRNA-seq was employed to analyze over 130,000 single-MSC transcriptomes.
• MSCs were sourced from clinically relevant tissues: bone marrow, adipose, umbilical cord, and dermis.
• High-quality transcriptomic data was used to identify MSC subpopulations and their gene-expression signatures.

Main Results:

• Seven tissue-specific and five conserved MSC subpopulations were identified with distinct gene-expression signatures.
• Extracellular matrix (ECM) was found to be a major contributor to MSC heterogeneity.
• Tissue-specific subpopulations exhibited heterogeneity in ECM-associated immune regulation, antigen processing, and senescence, influencing inter-donor and intra-tissue variability.
• The umbilical-cord-specific subpopulation demonstrated superior immunosuppressive properties.

Conclusions:

• This study provides significant insights into MSC heterogeneity across multiple levels.
• The developed MSC atlas taxonomy enhances the understanding of cellular heterogeneity.
• The findings reveal potential strategies for improving MSC-based therapeutic efficacy.