Abstract
Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative medicine and the treatment of autoimmune disorders. Comparing MSCs from different tissues at the single-cell level is fundamental for optimizing clinical applications. Here we analyzed single-cell RNA-seq data of MSCs from four tissues, namely umbilical cord, bone marrow, synovial tissue, and adipose tissue. We identified three major cell subpopulations, namely osteo-MSCs, chondro-MSCs, and adipo/myo-MSCs, across all MSC samples. MSCs from the umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. MSC subpopulations, with different subtypes and tissue sources, showed pronounced differences in differentiation potentials. After we compared the cell subpopulations and cell status pre-and-post chondrogenesis induction, osteogenesis induction, and adipogenesis induction, respectively, we found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at the single-cell level and subpopulation level, providing better targets for improving induction efficiency.
Highlights
Mesenchymal stem/stromal cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types including chondrocytes, osteocytes, myocytes, and adipocytes in vivo and in vitro (Pittenger et al, 1999; Dominici et al, 2006; Salem and Thiemermann, 2010)
We identified the 3 major cell subpopulations on Uniform Manifold Approximation and Projection (UMAP) projection after we integrated the four MSC samples (Figure 1A)
The three MSC subpopulations exhibited lineage-specific expression, namely chondrocyte lineage (HMGB1, HMGB2, DCN, F3, MDK, BMP5, KIAA0101), adipocyte/myocyte lineage (FTL, FTH1, TAGLN, FKBP1A, ACTG2, TXN) and osteoblast lineage (BGN, HAPLN1, FHL1, VCAN, GDF15) (Figure 1C, Supplementary Figures S1B, S1D, S1F, S1H and Supplementary Table S2)
Summary
Mesenchymal stem/stromal cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types including chondrocytes, osteocytes, myocytes, and adipocytes in vivo and in vitro (Pittenger et al, 1999; Dominici et al, 2006; Salem and Thiemermann, 2010). MSCs have been identified in most tissues in our body and could be isolated from bone marrow, umbilical cord, adipose tissue, synovial tissue, muscle, liver, dental pulp, and so on Prockop (1997), Zuk et al (2002), Romanov et al (2003), Wang et al (2004). It remains largely unexplored whether MSC subpopulations are consistent across tissues. Investigating the response of MSCs to various inductions at single-cell resolution could greatly facilitate our understanding of the processes and aid in developing efficient induction approaches
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