Biochemistry

   

Production of Functional Gametes from Somatic Cells of the Planarian Schmidtea Mediterranea Via in Vitro Gametogenesis

Authors: Jaba Tkemaladze, Gabro Gakely, Laura Gegelia, Iason Papadopulo, Alexander Taktakidze, Nino Metreveli, Natia Berozashvili, Natalia Bondarenko, Ucha Maglakelidze

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.

Comments: 25 Pages.

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[v1] 2025-09-15 19:51:12

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