Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory
Stem Cell Reports article from the Hörmanseder lab, with collaborations from the Hamperl and Scialdone labs
13.03.2025
Tomas Zikmund, Jonathan Fiorentino, Chris Penfold, Marco Stock, Polina Shpudeiko, Gaurav Agarwal, Larissa Langfeld, Kseniya Petrova, Leonid Peshkin, Stephan Hamperl, Antonio Scialdone, Eva Hoermanseder (2025 Mar 13) Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory. Stem Cell Reports. Open Access. https://doi.org/10.1016/j.stemcr.2025.102447
Summary cited directly from the article:
Nuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low, and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogramming in vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We findsubsets of reprogramming-resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning.Reducing expression levels of genes specific to the cell type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogram in vivo is cell type specific and emphasizes the necessity of minimizing aberrant transcripts of the previous somatic identity for improving reprogramming.