Cell Sub-Journal: Intuitive display of single cell X chromosome inactivation

Scientists have developed a new mouse model that can visually display the maternal / paternal X chromosome inactivation pattern at the level of a single cell.

In the cells of female true mammals (eutherian), one of the two X chromosomes is inactivated. These animals can use this mechanism to epigenetically regulate about 4% of gene expression in the genome. The coat color of the variegated cat can show the inactivation of the X chromosome, but it is not clear how this inactivation mechanism affects disease and development.

Now, the research team led by Jeremy Nathans of Johns Hopkins University School of Medicine has established a transgenic mouse model that can quantitatively display the X chromosome inactivation pattern at the level of a single cell. This result was published in Neuron magazine under Cell.

To establish this mouse model, the researchers inserted two fluorescent reporter genes (green fluorescent protein GFP and red fluorescent protein tdTomato) located in the nucleus into the X-linked Hprt locus. The expression of these reporter genes was affected by Cre ’s Induce. They hybridized two fluorescently-labeled mice so that their offspring female mice possessed two fluorescent X chromosomes, one green and one red.

The researchers then activated Cre expression through tissue-specific promoters to selectively analyze the red-green fluorescence in the cells. They analyzed the X chromosome inactivation pattern in various cells of the central nervous system, and also studied the X chromosome inactivation of retinal vascular disease through the Norrie disease model. Studies have shown that the pattern of X chromosome inactivation varies greatly between different tissues or cells.

The researchers pointed out that changes in the X chromosome inactivation pattern can introduce biodiversity into the central nervous system and may also cause some X-linked diseases (such as retinopathy).

"In the brain, diversity is the most important issue," Nathans introduced. He pointed out that diverse gene expression patterns can help the brain process information.

The author emphasizes in the article that this mouse model can be used for a variety of studies. For example, the pattern of X chromosome inactivation can be observed during mouse development. It is also possible to sort cells with mutations in the X chromosome and compare their gene expression with normal cells.

Next, scientists at Johns Hopkins University will continue to explore the mechanism of X chromosome inactivation and its impact on biological processes.

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