Understand cell types and how diseases develop

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Cellular function in tissues depends on the local environment. Mapping the molecular properties of cells while acquiring their exact location within a tissue is essential for a better understanding of disease.

The emergence of spatial transcriptomics has enabled the mapping of gene expression at the genome scale. Yet the ability to capture spatial epigenetic information from tissues at the cellular and genome-wide level is lacking. Now, a team of researchers from Yale and Karolinska Institutet has developed technology for spatial resolution chromatin accessibility profiling of tissue sections. The method could help create detailed molecular atlases of individual cells in different tissues and aims to better understand how diseases develop.

The method defines which regions of chromatin are genome-wide accessible in cells at specific locations in a tissue.

Gene activation requires this accessibility to chromatin, which offers distinct information about the molecular state of a particular cell. A significant advance in understanding cell identity, cell state and the underlying mechanisms that control gene expression – known as epigenetics – in the development of various tissues or diseases is the ability to combine the analysis of chromatin accessibility with the spatial location of cells. .

Rong Fan, professor of biomedical engineering at Yale, said: “Now we can identify cell types to build a spatial cell atlas based on chromatin accessibility. We can directly see cell types at an epigenetic level for better definition of cell states or to discover cell types.

The scientists profiled the mouse and human tissues using a method called “spatial-ATAC-seq.” Using this method on brain tissue has allowed scientists to see how intricately various regions of the brain develop. To better understand the organization of immune cell types, they also applied it to human tonsil tissue.

fan said, “We will get an unbiased overview and a much finer resolution view of all possible cell states and, more importantly, we will ‘see’ where they are in the tissues. It is a powerful tool for creating cell maps and cell atlases.

Yanxiang Deng, postdoctoral associate in Fan’s lab and lead author of the study, said that using the new method, they could identify the epigenome of cell types in mouse brain tissue in their original location.

Goncalo Castelo-Branco, professor of glial cell biology at Karolinska Institutet, said: “The application of spatial ATAC-Seq in diseased tissues could allow us in the near future to identify transitions between epigenetic states in specific cells in the context of the disease niche, which will provide insight into the molecular mechanisms involved in the acquisition of pathological cellular states. ”

Journal reference:

  1. Deng, Y., Bartosovic, M., Ma, S. et al. Spatial profiling of chromatin accessibility in murine and human tissues. Nature (2022). DOI: 10.1038/s41586-022-05094-1

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