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Zikmund, T. ; Fiorentino, J. ; Penfold, C.* ; Stock, M. ; Shpudeiko, P. ; Agarwal, G.* ; Langfeld, L. ; Petrova, K.* ; Peshkin, L.* ; Hamperl, S. ; Scialdone, A. ; Hörmanseder, E.

Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory.

Stem Cell Rep. 20:102447 (2025)

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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 find subsets 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Xenopus ; Early Embryonic Development ; In Vivo Reprogramming ; Mucocilliary Epithelium ; Nuclear Transfer ; Single Cell Rnaseq; Nuclear Transfer; Trichostatin; Efficiency; Genes

ISSN (print) / ISBN 2213-6711

Journal Stem Cell Reports

Quellenangaben Volume: 20, Issue: 4, Article Number: 102447

Publisher Cell Press

Publishing Place Maryland Heights, MO

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epigenetics and Stem Cells (IES)
Institute of Functional Epigenetics (IFE)
Institute of Computational Biology (ICB)

Grants Helmholtz Munich epigenetics summer internship program
Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary Life Science