title: CD49f Acts as an Inflammation Sensor to Regulate Differentiation, Adhesion, and Migration of Human Mesenchymal Stem Cells.
abstract: The advent of mesenchymal stem cell (MSC)-based therapies has been an exciting innovation for the treatment of degenerative and inflammatory diseases. However, the surface markers that accurately reflect the self-renewal and differentiation potential of MSCs and their sensitivity to environmental cues remain poorly defined. Here, we studied the role of CD49f in bone marrow MSCs (BMSCs) and the mechanism by which it regulates the behavior of BMSCs under inflammatory conditions. We found that CD49f is preferentially expressed in fetal cells rather than adult cells, CD49f-positive BMSCs possess higher CFU-F formation ability and differentiation potential than CD49f negative cells, and the CD49f expression of BMSCs gradually decreases during in vitro passaging. CD49f knockdown dramatically decreased the differentiation of BMSCs and isoform A was demonstrated to be the main functional form that enhanced the differentiation ability of BMSCs. The influences of inflammatory cytokines on BMSCs revealed that TNF-α downregulated CD49f in BMSCs with impaired differentiation, decreased adhesion to laminins, and increased migration. Moreover, tissue transglutaminase was found to work together with CD49f to regulate the behavior of BMSCs. Finally, we showed that mTOR signaling rather than NF-κB activation mediated CD49f downregulation induced by TNF-α and maintained CD49f homeostasis in BMSCs. Our findings suggest that CD49f is a stemness marker of BMSCs and is tightly correlated with the behavioral changes of BMSCs under inflammatory conditions. These data demonstrate a novel role for CD49f in sensing inflammation through mTOR pathway to further modulate the behavior of MSCs to fulfill the requirements of the body.
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Qiuchen
authors.initials: Q
authors.lastname: Li
authors.affiliation: 307-Ivy Translational Medicine Center, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Shize
authors.initials: S
authors.lastname: Ma
authors.affiliation: 307-Ivy Translational Medicine Center, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Wu
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union of Medical College, Beijing, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Xiao
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D039503:Integrin alpha6 / Q000096:biosynthesis*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D039503:Integrin alpha6
keywords: Alpha6 Integrin; Mammalian target of rapamycin; Mesenchymal Stem Cells; TNFalpha; Tissue transglutaminase