Jumping genes and development
An EU research project has investigated how the genomes of cells in the body, somatic cells, become varied and form a mosaic. One source is the action of jumping genes or transposable elements (TEs).
Retrotransposons are mobile genetic elements spread throughout genomes
and at least half the human genetic material is derived from these
transposable elements (TEs). Long interspersed elements (LINEs) are TEs
that are active in the human brain, generating variation in neuronal
genomes.
Recent research by the SOMATIC_MOSAICISM (LINE-1 retrotransposition in human somatic cells) project indicates that LINE activity occurs in pluripotent stem cells during embryo development. The researchers have developed a mouse model to determine if and how LINEs are active in all three germ layers – endoderm, mesoderm and ectoderm.
The scientists carried out retrotransposition assays in different tissue stem cells including human embryonic stem cells (hESCs) and neural progenitor cells (NPCs). Interestingly they only found high levels of retrotransposition in the NPCs themselves and those differentiated into mature neurons. This is highly significant as it is proof of somatic retrotransposition in non-dividing neurons.
Characterisation of the RNA and protein levels in the different germ layers following expression of LINEs showed that NPCs moderately express LINE-1 RNA and protein. However, the other germ layers showed much lower levels, which could explain how NPCs sustain high levels of somatic retrotransposition.
The SOMATIC_MOSAICISM team also mapped several new LINE-1 insertions in hESCs with a new protocol. This will enable detection of hot spots of insertion dependent on the germ layer in future work planned by the team. Development of new hESC cell lines that enable inducible LINE-1 retrotransposition will pinpoint the genes involved.
SOMATIC_MOSAICISM research has provided a strong knowledge platform for the discovery of new ways in which genetic plasticity is incorporated into the human genome. Consequent changes in gene expression could not only generate variation but cause neurological diseases and some cancers.
published: 2016-06-15