2024/04/23 by Liming Gui, Qin Zhong, Jue Yang +5
Biochemistry, Genetics and Molecular Biology · Medicine · #Pluripotent Stem Cells Research #Renal and related cancers #Reproductive Biology and Fertility
paper · doi:10.1093/stmcls/sxae029
openalex publication_date 2024/04/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Fully grown oocytes have the natural ability to transform 2 terminally differentiated gametes into a totipotent zygote representing the acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1, Zar1, Padi6, and Npm2, designated as MFiTLSCs. MFiTLSCs exhibited a unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodeled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance the understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for the development of oocyte biology-based reprogramming technology.