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.

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

Negri, Stefano;
2020-01-01

Abstract

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.
2020
CD107a/LAMP1
adipogenesis
exocytosis
human
medicine
mesenchymal stem cell
mouse
osteogenesis
perivascular stem cell
rat
regenerative medicine
stem cells
Adipocytes
Adipogenesis
Animals
Cell Differentiation
Humans
Lysosomal-Associated Membrane Protein 1
Male
Mesenchymal Stem Cells
Mice
Mice, Inbred NOD
Mice, SCID
Osteogenesis
Rats
Rats, Nude
Stem Cells
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1062396
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