{"title":"细胞类型依赖性转化生长因子-β信号在出生后神经干细胞增殖和迁移中的作用。","authors":"Kierra Ware, Joshua Peter, Lucas McClain, Yu Luo","doi":"10.4103/NRR.NRR-D-24-00623","DOIUrl":null,"url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202603000-00039/figure1/v/2025-06-16T082406Z/r/image-tiff Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo , we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in ( mGFAPcre - ALK5fl/fl - Ai9 ) or immature neuroblasts in ( DCXcreERT2 - ALK5fl/fl - Ai9 ). Our data showed that exogenous transforming growth factor-β treatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration. These effects were abolished in activin-like kinase 5 (ALK5) knockout primary neural stem cells. Consistent with this, inhibition of transforming growth factor-β signaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells. Interestingly, deletion of transforming growth factor-β receptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre - ALK5fl/fl - Ai9 mice, while abolishment of transforming growth factor-β signaling in immature neuroblasts in DCXcreERT2 - ALK5fl/fl - Ai9 mice did not affect the migration of these cells in the hippocampus. In summary, our data supports a dual role of transforming growth factor-β signaling in the proliferation and migration of neural stem cells in vitro . Moreover, our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-β signaling on neural stem cell proliferation and migration in vivo .</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1151-1161"},"PeriodicalIF":5.9000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cell type-dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration.\",\"authors\":\"Kierra Ware, Joshua Peter, Lucas McClain, Yu Luo\",\"doi\":\"10.4103/NRR.NRR-D-24-00623\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>JOURNAL/nrgr/04.03/01300535-202603000-00039/figure1/v/2025-06-16T082406Z/r/image-tiff Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo , we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in ( mGFAPcre - ALK5fl/fl - Ai9 ) or immature neuroblasts in ( DCXcreERT2 - ALK5fl/fl - Ai9 ). Our data showed that exogenous transforming growth factor-β treatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration. These effects were abolished in activin-like kinase 5 (ALK5) knockout primary neural stem cells. Consistent with this, inhibition of transforming growth factor-β signaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells. Interestingly, deletion of transforming growth factor-β receptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre - ALK5fl/fl - Ai9 mice, while abolishment of transforming growth factor-β signaling in immature neuroblasts in DCXcreERT2 - ALK5fl/fl - Ai9 mice did not affect the migration of these cells in the hippocampus. In summary, our data supports a dual role of transforming growth factor-β signaling in the proliferation and migration of neural stem cells in vitro . Moreover, our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-β signaling on neural stem cell proliferation and migration in vivo .</p>\",\"PeriodicalId\":19113,\"journal\":{\"name\":\"Neural Regeneration Research\",\"volume\":\" \",\"pages\":\"1151-1161\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2026-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neural Regeneration Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4103/NRR.NRR-D-24-00623\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neural Regeneration Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/NRR.NRR-D-24-00623","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/29 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Cell type-dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration.
JOURNAL/nrgr/04.03/01300535-202603000-00039/figure1/v/2025-06-16T082406Z/r/image-tiff Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo , we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in ( mGFAPcre - ALK5fl/fl - Ai9 ) or immature neuroblasts in ( DCXcreERT2 - ALK5fl/fl - Ai9 ). Our data showed that exogenous transforming growth factor-β treatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration. These effects were abolished in activin-like kinase 5 (ALK5) knockout primary neural stem cells. Consistent with this, inhibition of transforming growth factor-β signaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells. Interestingly, deletion of transforming growth factor-β receptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre - ALK5fl/fl - Ai9 mice, while abolishment of transforming growth factor-β signaling in immature neuroblasts in DCXcreERT2 - ALK5fl/fl - Ai9 mice did not affect the migration of these cells in the hippocampus. In summary, our data supports a dual role of transforming growth factor-β signaling in the proliferation and migration of neural stem cells in vitro . Moreover, our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-β signaling on neural stem cell proliferation and migration in vivo .
期刊介绍：
Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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