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.
Competing Interests: JX, YW, CH, SN, RT, YG, YT, TS, CM, WH, LC, SH, NK, KB No competing interests declared, BP BP is the inventor of perivascular stem cell related patents held by the UC Regents (Patent number: 9730965) and is on the editorial board of Stem Cells. AJ AWJ is a paid consultant for Novadip. This arrangement has been reviewed and approved by the JHU in accordance with its conflict of interest polices. AWJ receives funding for unrelated research from MTF Biologics and Novadip, and is on the editorial board of American Journal of Pathology and Bone Research. AWJ is the inventor of methods to purify CD107a progenitor cells held by the Johns Hopkins University.
(© 2020, Xu et al.)