Cell Fate Changes: The Role of Transcriptional Memory in Reprogramming
A research team led by Dr. Eva Hörmanseder from the Institute of Epigenetics and Stem Cells (IES) has uncovered crucial factors that limit the success of nuclear reprogramming, a process used to change one type of cell into another. While this technique holds great promise for regenerative medicine, it often leads to cells that do not function properly.
Tracking Reprogramming in Living Cells
By using nuclear transfer to eggs, the scientists were able to follow individual cells during the reprogramming process inside a living organism. This allowed them to pinpoint key factors that determine whether a cell successfully transforms into its new identity.
The study finds that reprogramming efficiency in vivo is heterogeneous across cell types, and that some cells hold onto transcriptional memories of their previous identity, making transformation difficult. Certain cells resist change altogether, either failing to become functional or disrupting normal body development.
Improving Reprogramming Success
Importantly, the researchers discovered that interfering with the activity of genes tied to the original cell type can significantly improve reprogramming outcomes. By minimizing lingering transcription factors from the cell’s previous identity, they achieved better transformation and increased functionality in the new cell type.
“These findings mark a major advance in understanding why some cells reprogram effectively while others fail,” said Eva Hörmanseder, the senior author of the study. “By identifying and addressing the roadblocks to reprogramming, we can develop better techniques for generating healthy, functional cells. This has profound implications for regenerative medicine and future treatments.”
Towards Better Cell-Based Therapies
This study highlights the importance of resetting a cell’s identity to optimize reprogramming. The insights gained could lead to more effective methods for developing lab-grown tissues, improving disease models, and advancing cell-based therapies for conditions like organ failure and neurodegenerative diseases.
Original Publication
Zikmund et al., 2025: Differentiation Success of Reprogrammed Cells is Heterogenous In Vivo and Modulated by Somatic Cell Identity Memory. Stem Cell Reports. DOI: 10.1016/j.stemcr.2025.102447