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

Jiajia Xu, Yiyun Wang, Ching-yun Hsu, Stefano Negri, Robert J Tower, Yongxing Gao, Ye Tian, Takashi Sono, Carolyn A Meyers, Winters R Hardy, Leslie Chang, Shuaishuai Hu, Nusrat Kahn, Kristen Broderick, Bruno Péault, Aaron W James

Research output: Contribution to journalArticlepeer-review

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, CD107alow cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107ahigh cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107alow cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107ahigh cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107alow cells are precursors of CD107ahigh 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.
Original languageEnglish
Article numbere58990
Number of pages30
JournaleLIFE
Volume9
Issue number10
Early online date12 Oct 2020
DOIs
Publication statusE-pub ahead of print - 12 Oct 2020

Fingerprint

Dive into the research topics of 'Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells'. Together they form a unique fingerprint.

Cite this