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

1
Department of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan
2
Division of Dentistry and Oral Surgery, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan
3
Department of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2021, 9(3), 278; https://doi.org/10.3390/biomedicines9030278
Received: 9 February 2021 / Revised: 7 March 2021 / Accepted: 8 March 2021 / Published: 10 March 2021
(This article belongs to the Section Gene and Cell Therapy)
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. View Full-Text
Keywords: mesenchymal stem cell; stem cell; niche; junctional adhesion molecule; tight junction; shedding mesenchymal stem cell; stem cell; niche; junctional adhesion molecule; tight junction; shedding
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MDPI and ACS Style

Yamazaki, M.; Sugimoto, K.; Mabuchi, Y.; Yamashita, R.; Ichikawa-Tomikawa, N.; Kaneko, T.; Akazawa, C.; Hasegawa, H.; Imura, T.; Chiba, H. Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells. Biomedicines 2021, 9, 278. https://doi.org/10.3390/biomedicines9030278

AMA Style

Yamazaki M, Sugimoto K, Mabuchi Y, Yamashita R, Ichikawa-Tomikawa N, Kaneko T, Akazawa C, Hasegawa H, Imura T, Chiba H. Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells. Biomedicines. 2021; 9(3):278. https://doi.org/10.3390/biomedicines9030278

Chicago/Turabian Style

Yamazaki, Morio, Kotaro Sugimoto, Yo Mabuchi, Rina Yamashita, Naoki Ichikawa-Tomikawa, Tetsuharu Kaneko, Chihiro Akazawa, Hiroshi Hasegawa, Tetsuya Imura, and Hideki Chiba. 2021. "Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells" Biomedicines 9, no. 3: 278. https://doi.org/10.3390/biomedicines9030278

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