Zhou Hai, Zeng Zhen, Koentgen Frank, Khan Mona, Mombaerts Peter
Max Planck Research Unit for Neurogenetics, Frankfurt, Germany.
Ozgene Pty Ltd, Bentley, Western Australia, Australia.
Genesis. 2019 Jun;57(6):e23295. doi: 10.1002/dvg.23295. Epub 2019 Apr 19.
Spermatogonial stem cells (SSCs) are adult stem cells that are slowly cycling and self-renewing. The pool of SSCs generates very large numbers of male gametes throughout the life of the individual. SSCs can be cultured in vitro for long periods of time, and established SSC lines can be manipulated genetically. Upon transplantation into the testes of infertile mice, long-term cultured mouse SSCs can differentiate into fertile spermatozoa, which can give rise to live offspring. Here, we show that the testicular soma of mice with a conditional knockout (conKO) in the X-linked gene Tsc22d3 supports spermatogenesis and germline transmission from cultured mouse SSCs upon transplantation. Infertile males were produced by crossing homozygous Tsc22d3 floxed females with homozygous ROSA26-Cre males. We obtained 96 live offspring from six long-term cultured SSC lines with the aid of intracytoplasmic sperm injection. We advocate the further optimization of Tsc22d3-conKO males as recipients for testis transplantation of SSC lines.
精原干细胞（SSCs）是成年干细胞，它们进行缓慢的细胞周期循环并自我更新。在个体的一生中，精原干细胞库会产生大量的雄配子。精原干细胞可以在体外长期培养，并且已建立的精原干细胞系可以进行基因操作。将长期培养的小鼠精原干细胞移植到不育小鼠的睾丸中后，它们可以分化为可育的精子，进而产生活的后代。在此，我们表明，在X连锁基因Tsc22d3中具有条件性敲除（conKO）的小鼠的睾丸体细胞，在移植后支持培养的小鼠精原干细胞的精子发生和种系传递。通过将纯合的Tsc22d3floxed雌性小鼠与纯合的ROSA26-Cre雄性小鼠杂交，产生了不育雄性小鼠。借助胞浆内精子注射，我们从6个长期培养的精原干细胞系中获得了96个活的后代。我们主张进一步优化Tsc22d3-conKO雄性小鼠作为精原干细胞系睾丸移植的受体。
