Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells
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, CD107alowcells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107ahighcells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107alowcells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107ahighcells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107alowcells are precursors of CD107ahighcells. 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 12, 2020
- Source ID
- 10.7554/elife.58990
Entities
People
- Aaron W James
- Bruno Peault
- Carolyn A. Meyers
- Ching-yun Hsu
- Jiajia Xu
- Kristen Broderick
- Leslie Chang
- Nusrat Kahn
- Robert J. Tower
- Shuaishuai Hu
- Stefano Negri
- Takashi Sono
- Winters R Hardy
- Ye Tian
- Yiyun Wang
- Yongxing Gao
Organizations
- American Cancer Society
- British Heart Foundation
- China Medical University
- Johns Hopkins University
- Maryland Stem Cell Research Fund
- Musculoskeletal Transplant Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research
- United States Department of Defense
- University of California, Los Angeles
- University of Edinburgh