Acquisition of 2C-like totipotency through defined maternal-effect factors

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Reproductive Biology

Background:

• Oocytes naturally reprogram differentiated gametes into totipotent zygotes.
• This reprogramming depends on maternal-effect factors (MFs) stored within the egg.
• MFs hold potential for inducing cellular reprogramming to a totipotent state.

Purpose of the Study:

• To generate totipotent-like stem cells (MFiTLSCs) from mouse embryonic stem cells (mESCs).
• To investigate the reprogramming potential of specific maternal-effect factors (Hsf1, Zar1, Padi6, Npm2).
• To understand the mechanisms underlying totipotency establishment and cell fate determination.

Main Methods:

• Generation of MFiTLSCs from mESCs using four specific maternal-effect factors.
• Assessment of MFiTLSC differentiation potential into embryonic and extraembryonic lineages.
• Transcriptomic analysis to identify key genes and regulatory states in MFiTLSCs.

Main Results:

• Successfully generated MFiTLSCs exhibiting totipotent-like characteristics.
• MFiTLSCs demonstrated the ability to differentiate into diverse embryonic and extraembryonic derivatives.
• Transcriptomic data revealed enrichment of 2-cell-specific genes, promoting a poised transcriptional repression state.

Conclusions:

• The derived MFiTLSCs provide a novel model for studying totipotent stem cells.
• This method advances understanding of cellular reprogramming and totipotency acquisition.
• Establishes a foundation for oocyte biology-based reprogramming technologies.