Production of Functional Gametes from Somatic Cells of the Planarian Schmidtea Mediterranea Via in Vitro Gametogenesis
DOI:
https://doi.org/10.5281/zenodo.17131383Keywords:
In Vitro Gametogenesis, IVG, Planarian, Schmidtea Mediterranea, Direct Reprogramming, Germ Cell, Transdifferentiation, Somatic Cell, ReprogrammingAbstract
This study establishes a novel and robust protocol for the direct reprogramming of differentiated somatic cells into functional gamete precursors in the planarian Schmidtea mediterranea, bypassing the need for a pluripotent intermediate state. Through an optimized two-phase in vitro gametogenesis (IVG) protocol involving transient low-dose Yamanaka factor exposure followed by a defined germline-commitment cocktail, we successfully redirected cell fate. Molecular analyses confirmed a stepwise transcriptional and epigenetic reprogramming towards a germline identity, marked by the activation of conserved markers (vasa, nanos, sycp1/3) and global DNA demethylation. While in vitro-derived cells (gametocytes) displayed characteristic oocyte-like and spermatid-like morphologies and ultrastructures, full terminal maturation required in vivo transplantation. Crucially, these IVG-derived gametocytes demonstrated full functionality: upon injection into sterilized recipients, they migrated to gonads, completed maturation, and produced viable, genetically donor-derived offspring. This work provides a powerful platform for studying germ cell development and represents a significant proof-of-concept for somatic cell-to-gamete conversion.
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