Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males.
Donor-derived spermatogenesis following stem cell transplantation in sterile NANOS2 knockout males.
复制标题
DOI：
10.1073/pnas.2010102117
复制
发表时间：
2020-09-29
影响因子：
11.1
通讯作者：
Oatley JM
中科院分区：
文献类型：
--
作者：
Ciccarelli M;Giassetti MI;Miao D;Oatley MJ;Robbins C;Lopez-Biladeau B;Waqas MS;Tibary A;Whitelaw B;Lillico S;Park CH;Park KE;Telugu B;Fan Z;Liu Y;Regouski M;Polejaeva IA;Oatley JM
将从供体雄性分离的产精子干细胞转移到受体雄性的睾丸中对于保存种质和作为在畜牧生产中广泛传播所需遗传学的管道具有重要的应用。一个关键的方面是缺乏内源性生殖系但在其他方面生理正常的替代雄性。在这里，我们证明了通过CRISPR-Cas9编辑NANOS 2基因使雄性小鼠、猪和山羊遗传不育，支持异基因干细胞移植后供体来源的精子发生。此外，我们还表明，牛中NANOS 2基因的CRISPR-Cas9编辑导致雄性生殖系消融。这些发现代表了代孕公畜成为所有哺乳动物传播和再生种质的工具的重大进展。精原干细胞移植（Spermatogonial stem cell transplantation，SSCT）是一种在供体和受体雄性之间进行生殖细胞转移的实验技术，可用作生物医学研究、濒危物种保护和在食用动物种群中传播所需遗传学的工具。为了充分实现这些潜力，受体男性必须缺乏内源性生殖系，但具有正常的睾丸结构和体细胞功能，能够支持异基因供体干细胞植入和精子发生的再生。在这里，我们表明，携带由CRISPR-Cas9编辑产生的NANOS 2基因敲除等位基因的雄性小鼠，猪，山羊和牛具有生殖系消融但其他结构正常的睾丸。在成年猪和山羊中，使用同种异体供体干细胞的SSCT导致持续的供体来源的精子发生。对于青春期前的小鼠，同种异体SSCT导致自然生育能力的实现。总的来说，这些进展代表了实现替代父系作为所有哺乳动物物种种质传播和再生工具的巨大潜力的重要一步。
Transfer of sperm-producing stem cells isolated from a donor male into testes of a recipient male has important applications for preserving germplasm and as a conduit for widespread dissemination of desirable genetics in livestock production. A key aspect is surrogate males that lack endogenous germline but are otherwise physiologically normal. Here we demonstrate that male mice, pigs, and goats rendered genetically sterile by CRISPR-Cas9 editing of the NANOS2 gene support donor-derived spermatogenesis following allogeneic stem cell transplantation. In addition, we show that CRISPR-Cas9 editing of the NANOS2 gene in cattle leads to male germline ablation. These findings represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals. Spermatogonial stem cell transplantation (SSCT) is an experimental technique for transfer of germline between donor and recipient males that could be used as a tool for biomedical research, preservation of endangered species, and dissemination of desirable genetics in food animal populations. To fully realize these potentials, recipient males must be devoid of endogenous germline but possess normal testicular architecture and somatic cell function capable of supporting allogeneic donor stem cell engraftment and regeneration of spermatogenesis. Here we show that male mice, pigs, goats, and cattle harboring knockout alleles of the NANOS2 gene generated by CRISPR-Cas9 editing have testes that are germline ablated but otherwise structurally normal. In adult pigs and goats, SSCT with allogeneic donor stem cells led to sustained donor-derived spermatogenesis. With prepubertal mice, allogeneic SSCT resulted in attainment of natural fertility. Collectively, these advancements represent a major step toward realizing the enormous potential of surrogate sires as a tool for dissemination and regeneration of germplasm in all mammalian species.
登录
查看更多内容
影响因子：
3.8
作者：
Herrid, Muren;Vignarajan, Soma;Hill, Jonathan R.
通讯作者：
Hill, Jonathan R.
使用 CRISPR/Cas9 系统有效敲除山羊基因
影响因子：
3.7
作者：
Ni W;Qiao J;Hu S;Zhao X;Regouski M;Yang M;Polejaeva IA;Chen C
通讯作者：
Chen C
纳米2基因的CRISPR/CAS9编辑生成种系的雄性猪。
影响因子：
4.6
作者：
Park KE;Kaucher AV;Powell A;Waqas MS;Sandmaier SE;Oatley MJ;Park CH;Tibary A;Donovan DM;Blomberg LA;Lillico SG;Whitelaw CB;Mileham A;Telugu BP;Oatley JM
通讯作者：
Oatley JM
DOI：
10.1146/annurev-animal-020518-115239
发表时间：
2019-01-01
期刊：
ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 7
影响因子：
--
作者：
Giassetti, Mariana I.;Ciccarelli, Michela;Oatley, Jon M.
通讯作者：
Oatley, Jon M.
影响因子：
3.6
作者：
Oatley, Melissa J.;Kaucher, Amy V.;Oatley, Jon M.
通讯作者：
Oatley, Jon M.