@article{c93fcc9f6cbf42c4b2fda335af094ed5,
title = "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, 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.",
author = "Jiajia Xu and Yiyun Wang and Hsu, {Ching Yun} and Stefano Negri and Tower, {Robert J.} and Yongxing Gao and Ye Tian and Takashi Sono and Meyers, {Carolyn A.} and Hardy, {Winters R.} and Leslie Chang and Shuaishuai Hu and Nusrat Kahn and Kristen Broderick and Bruno P{\'e}ault and James, {Aaron W.}",
note = "Funding Information: We thank the JHU microscopy core facility, JHMI deep sequencing and microarray core facility, and Hao Zhang within the JHU Bloomberg Flow Cytometry and Immunology Core. The slides of human adipose tissue depots used in Figure 1—figure supplement 2 were donated by Drs. Trivia Frazier and Jeffrey Gimble at Obatala Sciences, Inc (New Orleans LA). AWJ was supported by the NIH/ NIAMS (R01 AR070773, K08 AR068316), NIH/NIDCR (R21 DE027922), Department of Defense (W81XWH-18-1-0121, W81XWH-18-1-0336, W81XWH-18–10613), American Cancer Society (Research Scholar Grant, RSG-18-027-01-CSM), the Maryland Stem Cell Research Foundation, and MTF Biologics. In addition, MTF Biologics donated reagents for the study. This work was also supported by grants from BIRAX (the Britain Israel Research and Academic Exchange Partnership) and the British Heart Foundation (BHF) to BP. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health, Department of Defense, or U.S. Army. Funding Information: We thank the JHU microscopy core facility, JHMI deep sequencing and microarray core facility, and Hao Zhang within the JHU Bloomberg Flow Cytometry and Immunology Core. The slides of human adipose tissue depots used in Figure 1?figure supplement 2 were donated by Drs. Trivia Frazier and Jeffrey Gimble at Obatala Sciences, Inc (New Orleans LA). AWJ was supported by the NIH/ NIAMS (R01 AR070773, K08 AR068316), NIH/NIDCR (R21 DE027922), Department of Defense (W81XWH-18-1-0121, W81XWH-18-1-0336, W81XWH-18?10613), American Cancer Society (Research Scholar Grant, RSG-18-027-01-CSM), the Maryland Stem Cell Research Foundation, and MTF Biologics. In addition, MTF Biologics donated reagents for the study. This work was also supported by grants from BIRAX (the Britain Israel Research and Academic Exchange Partnership) and the British Heart Foundation (BHF) to BP. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health, Department of Defense, or U.S. Army. Publisher Copyright: {\textcopyright} Xu et al.",
year = "2020",
month = oct,
doi = "10.7554/eLife.58990",
language = "English (US)",
volume = "9",
pages = "1--30",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}