Germinal vesicles dissected from Xenopus meiotic oocytes containing potent factors to reprogram somatic cell nuclei.

Unlocking the potential for clinical application of reprogrammed somatic cells by germinal vesicles from Xenopus meiotic oocytes

01.03.2024 A study from the Gurdon lab led by Ming-Hsuan Wen defined the deterministic reprogramming of somatic cells to a totipotent-like state by Xenopus meiotic oocytes.

The study’s findings, which are scientifically significant, also have profound practical implications. The successful reprogramming of transplanted cells to a totipotent-like state through nuclear transfer, a process that can be completed in a day at 18ºC (metabolically equivalent to 4 hours at 37ºC), has been demonstrated in an in vitro culture system. This serves as a proof of concept for potential clinical use and could pave the way for developing commercially viable reprogrammed stem cell products.

Wen MH et al. Deterministic nuclear reprogramming of mammalian nuclei to a totipotency-like state by Amphibian meiotic oocytes for stem cell therapy in humans. Biol Open. 2024 Mar 1;13(3):bio060011. DOI: 10.1242/bio.060011.
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Fig. 1

The ultimate aim of nuclear reprogramming is to provide stem cells or differentiated cells from unrelated cell types as a cell source for regenerative medicine. A popular route towards this is transcription factor induction, and an alternative way is an original procedure of transplanting a single somatic cell nucleus to an unfertilized egg. A third route is to transplant hundreds of cell nuclei into the germinal vesicle (GV) of a non-dividing Amphibian meiotic oocyte, which leads to the activation of silent genes in 24 h and robustly induces a totipotency-like state in almost all transplanted cells. We apply this third route for potential therapeutic use and describe a procedure by which the differentiated states of cells can be reversed so that totipotency and pluripotency gene expression are regained. Differentiated cells are exposed to GV extracts and are reprogrammed to form embryoid bodies, which shows the maintenance of stemness and could be induced to follow new directions of differentiation. We conclude that much of the reprogramming effect of eggs is already present in meiotic oocytes and does not require cell division or selection of dividing cells. Reprogrammed cells by oocytes could serve as replacements for defective adult cells in humans.