Combined Omics Analysis Identifies Transmembrane 4 L6 Family Member 1 as a Surface Protein Marker Specific to Human Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are promising for cell therapy and regenerative medicine; but their lack of specific markers renders the cell culture at potential contamination risk with other cell types, in particular, fibroblasts. In this study, we mapped 2 differential transcriptome data of MSCs compared, one to mononuclear cells and the other to fibroblasts, onto the membrane proteome data, the analysis of which led to an identification of transmembrane 4 L6 family member 1 (TM4SF1) as a surface protein marker candidate that could discriminate MSCs simultaneously from blood cells and fibroblasts. Our analyses confirmed that TM4SF1 was abundantly expressed on MSCs but neither on other blood/tissue cells nor on fibroblasts. TM4SF1 immunoselection from bone marrow and adipose tissues yielded homogeneous cell populations that were highly similar to MSCs, in terms of morphology, immunophenotype, and differentiation potential. These findings indicate that TM4SF1 can serve as a surface protein marker which singly identifies MSCs from diverse cell sources, in particular, fibroblast-rich connective tissues.