What are the effects of genomic imprinting
Cell analysis shows: cells react differently to genomic imprinting
Previous studies showed that imprinted genes are more active in some tissues, but less active in others. The neuroscientists working with Hippenmeyer found that genes that are shaped in the cortex are also more strongly expressed in some cell types, i.e. more active than in other cell types.
In order to investigate the effect of this different gene activity, the researchers applied the MADM technique established by Hippenmeyer. "With this technology we can mark cells in color and at the same time increase or decrease the expression level of the genes," explains Susanne Laukoter. "In our experiments we doubled the expression of imprinted genes in some cells, in some we switched them off completely. We were able to observe at the individual cell level how cells react to the change in gene dose."
The researchers found that cells respond to changes in the dose of imprinted genes by activating certain gene groups - especially gene groups that are important for cell death, growth and the development of synapses. This response was strongest in the cell type of astrocytes, a form of glial cells that support the nerve cells.
A detailed analysis of the astrocytes showed that astrocytes with a double dose of some paternal genes are always present in higher numbers than astrocytes with a double dose of the corresponding maternal genes. This difference ran through the entire development of the brain. "Either the genomic imprinting protects cells from cell death with a double paternal gene dose, or double the maternal gene dose accelerates cell death," explains Florian Pauler.
Earlier studies suggested a connection between genomic imprinting and cell death, the recently published study now shows that this connection depends on the cell type and is particularly strong in astrocytes. Neurons with twice the number of maternal genes did not respond with cell death, instead they formed other connections and networks. "Each cell type reacts differently to the disomy, i.e. the presence of two maternal or two paternal genes," says Simon Hippenmeyer, explaining the result. That can be important for people too. "Prader-Willi syndrome and Angelman syndrome are caused by a duplication of a genomically shaped chromosome segment. Each organ reacts differently to the duplication. If we better understand the cell-type-specific reaction, a targeted therapy may hopefully be possible in the future become."
MEDICA.de; Source: Institute of Science and Technology Austria
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