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Updated: Jul 6, 2025
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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
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Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells
Matthew M Edwards1, Ning Wang2, Dashiell J Massey1
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Cell Reports
|January 9, 2024
Summary
DNA replication timing is not fully reprogrammed in induced pluripotent stem cells (iPSCs), potentially impacting cell therapy quality. This process, crucial for genome regulation, shows delays in some iPSCs compared to embryonic stem cells.
Area of Science:
- Stem cell biology
- Epigenetics
- Genome regulation
Background:
- Induced pluripotent stem cells (iPSCs) are vital for cell therapy.
- Differences in gene expression, DNA methylation, and chromatin exist between iPSCs and embryonic stem cells (ESCs).
- Efficient reprogramming of DNA replication timing in iPSCs remains largely uncharacterized.
Purpose of the Study:
- To compare genome-wide DNA replication timing between ESCs, iPSCs, and nuclear transfer-derived ESCs (NT-ESCs).
- To investigate whether DNA replication timing is fully reprogrammed to the embryonic state in iPSCs.
Main Methods:
- Genome-wide replication timing analysis.
- Comparison of replication timing profiles across ESCs, iPSCs, and NT-ESCs.
- Analysis of DNA methylation and gene expression in relation to replication timing.
Main Results:
- NT-ESCs exhibited DNA replication timing indistinguishable from ESCs.
- A subset of iPSCs displayed delayed DNA replication in heterochromatic regions.
- These replication delays were linked to downregulated genes with incomplete DNA methylation reprogramming and persisted after neuronal differentiation.
Conclusions:
- DNA replication timing reprogramming can be incomplete in iPSCs.
- Replication timing delays are resistant to reprogramming and differentiation.
- Incompletely reprogrammed DNA replication timing may affect iPSC quality for therapeutic applications.
Keywords:
CP: Molecular biologyCP: Stem cell researchDNA replication timingepigenetic aberrationsheterochromatininduced pluripotent stem cellssomatic cell nuclear transferstem cell differentiationMore Related Videos
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