Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells
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...
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MDPI AG
2021-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/3/278 |
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| author | Morio Yamazaki Kotaro Sugimoto Yo Mabuchi Rina Yamashita Naoki Ichikawa-Tomikawa Tetsuharu Kaneko Chihiro Akazawa Hiroshi Hasegawa Tetsuya Imura Hideki Chiba |
| author_facet | Morio Yamazaki Kotaro Sugimoto Yo Mabuchi Rina Yamashita Naoki Ichikawa-Tomikawa Tetsuharu Kaneko Chihiro Akazawa Hiroshi Hasegawa Tetsuya Imura Hideki Chiba |
| author_sort | Morio Yamazaki |
| collection | DOAJ |
| description | 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, <i>Cd44</i>, <i>Cd105</i>, <i>Cd140a</i>, <i>Cd166</i> and <i>Sca-1</i>, 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. |
| first_indexed | 2024-03-10T13:23:36Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-10T13:23:36Z |
| publishDate | 2021-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-ce66bdee6f0e49688b9747a5a05e9f6a2023-11-21T09:50:27ZengMDPI AGBiomedicines2227-90592021-03-019327810.3390/biomedicines9030278Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem CellsMorio Yamazaki0Kotaro Sugimoto1Yo Mabuchi2Rina Yamashita3Naoki Ichikawa-Tomikawa4Tetsuharu Kaneko5Chihiro Akazawa6Hiroshi Hasegawa7Tetsuya Imura8Hideki Chiba9Department of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, JapanDepartment of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDivision of Dentistry and Oral Surgery, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, JapanDivision of Dentistry and Oral Surgery, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, JapanJunctional 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, <i>Cd44</i>, <i>Cd105</i>, <i>Cd140a</i>, <i>Cd166</i> and <i>Sca-1</i>, 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.https://www.mdpi.com/2227-9059/9/3/278mesenchymal stem cellstem cellnichejunctional adhesion moleculetight junctionshedding |
| spellingShingle | Morio Yamazaki Kotaro Sugimoto Yo Mabuchi Rina Yamashita Naoki Ichikawa-Tomikawa Tetsuharu Kaneko Chihiro Akazawa Hiroshi Hasegawa Tetsuya Imura Hideki Chiba Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells Biomedicines mesenchymal stem cell stem cell niche junctional adhesion molecule tight junction shedding |
| title | Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells |
| title_full | Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells |
| title_fullStr | Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells |
| title_full_unstemmed | Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells |
| title_short | Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells |
| title_sort | soluble jam c ectodomain serves as the niche for adipose derived stromal stem cells |
| topic | mesenchymal stem cell stem cell niche junctional adhesion molecule tight junction shedding |
| url | https://www.mdpi.com/2227-9059/9/3/278 |
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