本帖最后由 ipsvirus 于 2015-6-26 15:01 编辑
Cell research：缺乏精子也能繁衍后代基因突变会导致精子缺乏，造成男性不育。由于睾丸中缺少功能性的生殖细胞，这些患者无法通过辅助生殖技术（比如IVF）拥有自己的后代，恢复他们的生育能力是一个很大的挑战。
南京医科大学、中科院动物研究所的科学家们日前在这一方面取得了重要突破。他们将细胞重编程和基因组编辑结合起来，成功让缺乏精子的突变小鼠生成了功能性精子，并且拥有了自己的后代。这一成果发表在六月十九日的Cell Research杂志上，文章的通讯作者是中科院动物所研究员周琪（Qi Zhou）、南京医科大学特聘教授沙家豪（Jiahao Sha）、和中科院动物所研究员赵小阳（Xiao-Yang Zhao）。
体细胞核移植主要是把供体细胞的细胞核移植到已去除细胞核的卵细胞中。通过这样的重编程，人们可以获得与供体细胞相匹配的胚胎。研究人员对Kitw/Kitwv小鼠模型的体细胞进行核移植，得到了核移植胚胎干细胞(ntESC)。
随后，他们用TALEN进行基因组编辑，矫正了ntESC中的基因突变，并将其进一步分化为类似原始生殖细胞的细胞（primordial germ cell-like cell，PGCLC）。研究显示，这些PGCLC可以在小鼠睾丸中生成功能性的精子，支持后代小鼠发育到足月。这项研究向人们展示了一条新途径，有助于解决基因突变造成的男性不育。
来源：生物通
Generation of fertile offspring from Kitw/Kitwv mice through differentiation of gene corrected nuclear transfer embryonic stem cells
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[size=12.960000038147px]Yan Yuan1,*, Quan Zhou1,*, Haifeng Wan2,*, Bin Shen1,*, Xuepeng Wang2,3, Mei Wang2,4, Chunjing Feng2,3, Mingming Xie2,5, Tiantian Gu2, Tao Zhou1, Rui Fu2, Xingxu Huang6, Qi Zhou2, Jiahao Sha1 and Xiao-Yang Zhao2
[size=12.960000038147px]
Genetic mutations could cause sperm deficiency, leading to male infertility. Without functional gametes in the testes, patients cannot produce progeny even with assisted reproduction technologies such as in vitro fertilization. It has been a major challenge to restore the fertility of gamete-deficient patients due to genetic mutations. In this study, using a Kitw/Kitwv mouse model, we investigated the feasibility of generating functional sperms from gamete-deficient mice by combining the reprogramming and gene correcting technologies. We derived embryonic stem cells from cloned embryos (ntESCs) that were created by nuclear transfer of Kitw/Kitwvsomatic cells. Then we generated gene-corrected ntESCs using TALEN-mediated gene editing. The repaired ntESCs could further differentiate into primordial germ cell-like cells (PGCLCs) in vitro. RFP-labeled PGCLCs from the repaired ntESCs could produce functional sperms in mouse testes. In addition, by co-transplantation with EGFP-labeled testis somatic cells into the testes where spermatogenesis has been chemically damaged or by transplantation into Kitw/Kitwv infertile testes, non-labeled PGCLCs could also produce haploid gametes, supporting full-term mouse development. Our study explores a new path to rescue male infertility caused by genetic mutations.
Keywords: male infertility; reprogramming; gene correction; germ cell specification; Kit mutation
http://www.nature.com/cr/journal/vaop/ncurrent/abs/cr201574a.html
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发表于 2015-6-26 14:56:50
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发表于 2015-6-26 15:18:37
发表于 2015-6-29 16:03:01
