The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.
Shohag BhargavaBrian CoxChristiana PolydorouVeronika GresakovaVladimir KorinekHynek StrnadRadislav SedlacekTrevor Allan EppKallayanee ChawengsaksophakPublished in: Scientific reports (2017)
Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.
Keyphrases
- cell cycle arrest
- induced apoptosis
- long non coding rna
- dna methylation
- poor prognosis
- gene expression
- endoplasmic reticulum stress
- cell death
- single cell
- body composition
- signaling pathway
- physical activity
- cell therapy
- embryonic stem cells
- pi k akt
- genome wide
- electronic health record
- stem cells
- big data
- radiation therapy
- mesenchymal stem cells
- sensitive detection
- quantum dots