Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells

Tissue resident mesenchymal stem/stromal cells (MSCs) occupy perivascular spaces. Profiling human adipose perivascular mesenchyme with antibody arrays identified 16 novel surface antigens, including endolysosomal protein CD107a. Surface CD107a expression segregates MSCs into functionally distinct subsets. In culture, CD107a^low cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107a^high cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107a^low cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107a^high cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107a^low cells are precursors of CD107a^high cells. These results document the molecular and functional diversity of perivascular regenerative cells, and show that relocation to cell surface of a lysosomal protein marks the transition from osteo- to adipogenic potential in native human MSCs, a population of substantial therapeutic interest.