| First Author | Lee YH | Year | 2019 |
| Journal | Theranostics | Volume | 9 |
| Issue | 22 | Pages | 6443-6465 |
| PubMed ID | 31588228 | Mgi Jnum | J:297206 |
| Mgi Id | MGI:6472032 | Doi | 10.7150/thno.35619 |
| Citation | Lee YH, et al. (2019) Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling. Theranostics 9(22):6443-6465 |
| abstractText | Forkhead box protein C1 (FOXC1) is known to regulate developmental processes in the skull and brain. Methods: The unique multipotent arachnoid-pia stem cells (APSCs) isolated from human and mouse arachnoid-pia membranes of meninges were grown as 3D spheres and displayed a capacity for self-renewal. Additionally, APSCs also expressed the surface antigens as mesenchymal stem cells. By applying the FOXC1 knockout mice and mouse brain explants, signaling cascade of FOXC1-STI-1-PrP(C) was investigated to demonstrate the molecular regulatory pathway for APSCs self-renewal. Moreover, APSCs implantation in stroke model was also verified whether neurogenic property of APSCs could repair the ischemic insult of the stroke brain. Results: Activated FOXC1 regulated the proliferation of APSCs in a cell cycle-dependent manner, whereas FOXC1-mediated APSCs self-renewal was abolished in FOXC1 knockout mice (FOXC1(-/-) mice). Moreover, upregulation of STI-1 regulated by FOXC1 enhanced cell survival and self-renewal of APSCs through autocrine signaling of cellular prion protein (PrP(C)). Mouse brain explants STI-1 rescues the cortical phenotype in vitro and induces neurogenesis in the FOXC1 (-/-) mouse brain. Furthermore, administration of APSCs in ischemic brain restored the neuroglial microenvironment and improved neurological dysfunction. Conclusion: We identified a novel role for FOXC1 in the direct regulation of the STI-1-PrP(C) signaling pathway to promote cell proliferation and self-renewal of APSCs. |
