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

• Published in: eLife Vol. 9
• Main Authors: Xu, Jiajia, Wang, Yiyun, Hsu, Ching-Yun, Negri, Stefano, Tower, Robert J, Gao, Yongxing, Tian, Ye, Sono, Takashi, Meyers, Carolyn A, Hardy, Winters R, Chang, Leslie, Hu, Shuaishuai, Kahn, Nusrat, Broderick, Kristen, Péault, Bruno, James, Aaron W
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 12.10.2020; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: Adipocytes - metabolism; adipogenesis; Adipogenesis - genetics; Animals; CD107a/LAMP1; Cell Differentiation - genetics; exocytosis; Humans; Lysosomal-Associated Membrane Protein 1 - genetics; Lysosomal-Associated Membrane Protein 1 - metabolism; Male; Medicine; mesenchymal stem cell; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred NOD; Mice, SCID; osteogenesis; Osteogenesis - genetics; perivascular stem cell; Rats; Rats, Nude; RNA sequencing; Stem cells; Stem Cells - metabolism; Stem Cells and Regenerative Medicine; mesenchymal stem cell; mouse; stem cells; adipogenesis; rat; regenerative medicine; perivascular stem cell; exocytosis; medicine; CD107a/LAMP1; osteogenesis; human
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.58990

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 cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107a cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107a cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107a cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107a cells are precursors of CD107a 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.