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Generation of Histocompatible Androgenetic Embryonic Stem Cells Using Spermatogenic Cells
Qingguo Zhao 1, Jianle Wang 1 2, Yu Zhang 1, Zhaohui Kou 1, Sheng Liu 1, Shaorong Gao 1 *
1National Institute of Biological Sciences, Beijing 102206, China
2State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
Androgenetic embryonic stem (aES) cells, produced by pronuclear transplantation, offer an important autologous pluripotent stem cell source. However, the isolation of aES cells, particularly individual-specific aES cells, using fertilized embryos has limited the practical applications of this technology in humans. In the present study, we applied a new approach, essentially described as somatic cell nuclear transfer (SCNT), and generated three types of aES cell lines using spermatogenic cells including primary spermatocytes (PS), round spermatids (RS) and mature spermatozoa (S) as donor cells, omitting the need to use fertilized embryos. Although abnormality of chimeras and absent germline competency indicated that all three types of aES cells exhibiting limited pluripotency, the epigenetic status of the aES cell lines tended to resemble normal ES cells during long-term culture and some parental-specific imprinted genes were expressed at levels comparable to those of normal ES cells. Furthermore, the histocompatibility of the aES cells was investigated by transplanting the differentiation progenies of the aES cells into MHC-matched and mismatched recipient mice. The results indicated that these aES cells were histocompatible with MHC-matched mice after transplantation. Our study provided evidence indicating that MHC-competent autologous aES cells could be generated from different spermatogenic cells using nuclear transfer into oocytes that could avoid using fertilized embryos.
