Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells

Biomedicines

Naoki Ichikawa-Tomikawa¹  Morio Yamazaki¹  Kotaro Sugimoto¹  Hideki Chiba¹  Tetsuya Imura¹  Rina Yamashita¹  Chihiro Akazawa²  Yo Mabuchi²  Hiroshi Hasegawa³  Tetsuharu Kaneko³ 

[1] Department of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan;Department of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;Division of Dentistry and Oral Surgery, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan;

关键词: mesenchymal stem cell;    stem cell;    niche;    junctional adhesion molecule;    tight junction;    shedding;   

DOI  :  10.3390/biomedicines9030278

来源: DOAJ

【 摘 要 】

Junctional adhesion molecules (JAMs) are expressed in diverse types of stem and progenitor cells, but their physiological significance has yet to be established. Here, we report that JAMs exhibit a novel mode of interaction and biological activity in adipose-derived stromal/stem cells (ADSCs). Among the JAM family members, JAM-B and JAM-C were concentrated along the cell membranes of mouse ADSCs. JAM-C but not JAM-B was broadly distributed in the interstitial spaces of mouse adipose tissue. Interestingly, the JAM-C ectodomain was cleaved and secreted as a soluble form (sJAM-C) in vitro and in vivo, leading to deposition in the fat interstitial tissue. When ADSCs were grown in culture plates coated with sJAM-C, cell adhesion, cell proliferation and the expression of five mesenchymal stem cell markers, Cd44, Cd105, Cd140a, Cd166 and Sca-1, were significantly elevated. Moreover, immunoprecipitation assay showed that sJAM-C formed a complex with JAM-B. Using CRISPR/Cas9-based genome editing, we also demonstrated that sJAM-C was coupled with JAM-B to stimulate ADSC adhesion and maintenance. Together, these findings provide insight into the unique function of sJAM-C in ADSCs. We propose that JAMs contribute not only to cell–cell adhesion, but also to cell–matrix adhesion, by excising their ectodomain and functioning as a niche-like microenvironment for stem and progenitor cells.

【 授权许可】

Unknown