Departments of Pathology, Johns Hopkins University, Baltimore, United States
Yiyun Wang
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Ching-Yun Hsu
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Stefano Negri
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Robert J Tower
Departments of Pathology, Johns Hopkins University, Baltimore, United States; Departments of Orthopaedics, Johns Hopkins University, Baltimore, United States
Yongxing Gao
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Ye Tian
Departments of Pathology, Johns Hopkins University, Baltimore, United States; Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, China
Takashi Sono
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Carolyn A Meyers
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Winters R Hardy
Departments of Pathology, Johns Hopkins University, Baltimore, United States; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, United States
Leslie Chang
Departments of Pathology, Johns Hopkins University, Baltimore, United States
Shuaishuai Hu
UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, United States
Nusrat Kahn
UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, United States
Kristen Broderick
Departments of Plastic Surgery, Johns Hopkins University, Baltimore, United States
Bruno Péault
UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, United States; Center For Cardiovascular Science and Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
Departments of Pathology, Johns Hopkins University, Baltimore, United States; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, United States
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.
