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Project

In-vitro differentiation of genetically modified murine spermatogonial stem cells (FWOKN312)

The capacity to undertake gain- or loss-of-function experiments is crucial for discerning the importance of genes and factors of interest that relate to the processes of germline proliferation and differentiation. It also holds great promise for generating gene-modified animal models. Already a few publications report the efficient genetic manipulation of spermatogonial stem cells (SSCs) by CRISPR-Cas9, with subsequent transplantation into sterilized mice to produce gametes carrying desired genetic traits. Other gene editing methods have been less successful, probably due to their lower transfection efficiency and higher complexity. The combination of gene editing and in-vitro spermatogenesis has not yet been reported, although it would be less timely and less costly than transplantation. Because achieving in-vitro spermatogenesis starting from adult cell suspensions is challenging, the aim of this project is to mix gene-modified SSCs with nursing primary testicular cells in a 3D bioprinted-mediated organoid model to produce haploid gametes. In the future, apart from having a purpose in fundamental research studies and improving agriculture, this approach may one day enable production of healthy gametes from a human individual with a genetic disease (such as Huntington's disease, cystic fibrosis, etc.) that can be corrected.
Date:1 Jan 2019 →  31 Dec 2019
Keywords:cell genetics
Disciplines:Endocrinology