Source cell-type epigenetic memory persists in induced pluripotent cells but is lost in subsequently derived germline cells
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View abstract on PubMed
Summary
This summary is machine-generated.Induced pluripotent stem cells (iPSCs) retain some source cell memory, but this is largely erased when they differentiate into germ-cell like cells (GCLCs). This suggests iPSC-derived GCLCs could be useful for in vitro gametogenesis to treat infertility.
Area Of Science
- Epigenetics
- Stem Cell Biology
- Developmental Biology
Background
- Epigenetic memory in induced pluripotent stem cells (iPSCs) can limit cell fate transitions in vitro.
- This memory is a concern for therapeutic applications, especially for iPSC-derived germline cells.
Purpose Of The Study
- To investigate the extent of epigenetic and transcriptomic memory during the transitions from somatic cells to iPSCs, and from iPSCs to germ-cell like cells (GCLCs).
- To assess the potential of iPSC-derived GCLCs for in vitro gametogenesis.
Main Methods
- Derived iPSCs from four mouse cell types (two somatic, two germ).
- Assessed iPSC similarity to ES cells and source cells using gene expression and DNA methylation.
- Induced iPSCs to form GCLCs and compared their epigenomic and transcriptomic profiles to endogenous germ cells.
Main Results
- iPSC lines retained residual gene expression and epigenetic patterns from their original differentiated cell types.
- However, derived GCLCs showed minimal residual epigenetic or transcriptomic memory of the original source cells.
- GCLCs derived in vitro largely recapitulated epigenetic programming and gene expression of endogenous germ cells.
Conclusions
- The in vitro derivation of iPSCs and subsequent GCLCs recapitulates in vivo epigenetic reprogramming.
- In vitro derived germline cells accurately reflect epigenetic and gene expression patterns of endogenous germ cells.
- iPSC-derived GCLCs show potential for in vitro gametogenesis as a therapeutic strategy for infertility.
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