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Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling
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....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771253/ https://www.ncbi.nlm.nih.gov/pubmed/31588228 http://dx.doi.org/10.7150/thno.35619 |
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author | Lee, Yi-Hui Lee, Hsu-Tung Chen, Chien-Lin Chang, Chi-Hao Hsu, Chung Y. Shyu, Woei-Cherng |
author_facet | Lee, Yi-Hui Lee, Hsu-Tung Chen, Chien-Lin Chang, Chi-Hao Hsu, Chung Y. Shyu, Woei-Cherng |
author_sort | Lee, Yi-Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6771253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-67712532019-10-06 Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling Lee, Yi-Hui Lee, Hsu-Tung Chen, Chien-Lin Chang, Chi-Hao Hsu, Chung Y. Shyu, Woei-Cherng Theranostics Research Paper 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. Ivyspring International Publisher 2019-08-15 /pmc/articles/PMC6771253/ /pubmed/31588228 http://dx.doi.org/10.7150/thno.35619 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Lee, Yi-Hui Lee, Hsu-Tung Chen, Chien-Lin Chang, Chi-Hao Hsu, Chung Y. Shyu, Woei-Cherng Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title | Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title_full | Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title_fullStr | Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title_full_unstemmed | Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title_short | Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP(C) signaling |
title_sort | role of foxc1 in regulating apscs self-renewal via sti-1/prp(c) signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771253/ https://www.ncbi.nlm.nih.gov/pubmed/31588228 http://dx.doi.org/10.7150/thno.35619 |
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