論文 - 詳細
| RRC ID | 50638 |
|---|---|
| 著者 | Watanabe S, Kanatsu-Shinohara M, Ogonuki N, Matoba S, Ogura A, Shinohara T. |
| タイトル | In Vivo Genetic Manipulation of Spermatogonial Stem Cells and Their Microenvironment by Adeno-Associated Viruses. |
| ジャーナル | Stem Cell Reports |
| Abstract |
Adeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem cells (SSCs) and their microenvironment via AAV1/9. AAV1/9 microinjected into the seminiferous tubules penetrated both the basement membrane and BTB, thereby transducing not only Sertoli cells and SSCs but also peritubular cells and Leydig cells. Moreover, when congenitally infertile KitlSl/KitlSl-d mouse testes with defective Sertoli cells received Kitl-expressing AAVs, spermatogenesis regenerated and offspring were produced. None of the offspring contained the AAV genome. Thus, AAV1/9 allows efficient germline and niche manipulation by penetrating the BTB and basement membrane, providing a promising strategy for the development of gene therapies for reproductive defects. |
| 巻・号 | 10(5) |
| ページ | 1551-1564 |
| 公開日 | 2018-5-8 |
| DOI | 10.1016/j.stemcr.2018.03.005 |
| PII | S2213-6711(18)30132-2 |
| PMID | 29628393 |
| PMC | PMC5995272 |
| MeSH | Animals Cellular Microenvironment* Dependovirus / metabolism* Genetic Techniques* Infertility, Male / pathology Kinetics Male Mice, Inbred C57BL Microinjections Neuraminidase / metabolism Serogroup Sertoli Cells / pathology Spermatogenesis Spermatogonia / cytology* Spermatogonia / metabolism Spermatozoa / cytology Stem Cell Factor / metabolism Stem Cells / cytology* Stem Cells / metabolism Testis / cytology |
| IF | 6.032 |
| 引用数 | 8 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | AxCANCre (RDB01748) |