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Updated: Jan 2, 2026
09:44
Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases
Published on: May 2, 2025
572
DNA synthesis is required for reprogramming mediated by stem cell fusion
Tomomi Tsubouchi1, Jorge Soza-Ried, Karen Brown
1Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Cell
|February 19, 2013
Summary
Embryonic stem cells (ESCs) in S/G2 phases enhance reprogramming of somatic cells. DNA synthesis in somatic nuclei is essential for this pluripotent conversion, indicating its critical role.
Area of Science:
- Stem cell biology
- Epigenetics
- Cellular reprogramming
Background:
- Embryonic stem cells (ESCs) can induce pluripotency in differentiated cells via cell fusion.
- The underlying mechanism of this rapid reprogramming is not well understood.
Purpose of the Study:
- To investigate the role of the cell cycle in the reprogramming capacity of mouse ESCs.
- To identify key molecular events during the reprogramming of somatic cells by ESCs.
Main Methods:
- Centrifugal elutriation to isolate mouse ESCs at specific cell cycle stages (S/G2).
- Heterokaryon and hybrid assays to assess reprogramming of lymphocytes and fibroblasts.
- BrdU pulse-labeling and DNA polymerase inhibition to study DNA synthesis during reprogramming.
Main Results:
- ESCs in S/G2 phases demonstrated enhanced reprogramming of somatic cells.
- Successful reprogramming correlated with precocious nucleotide incorporation in somatic nuclei.
- Somatic nuclei undergoing reprogramming incorporated BrdU within 24 hours post-fusion.
- Inhibition of DNA polymerase activity blocked pluripotent conversion.
Conclusions:
- The cell cycle phase of ESCs influences their reprogramming potential.
- Early DNA synthesis in somatic nuclei is a critical and essential event for epigenetic reprogramming.
- Nucleotide incorporation is a key early step in reprogramming somatic cells within ESC-heterokaryons.
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