New DNA sequencing method preserves cells’ areas inside tissues

Within advanced tissues similar to most cancers tumors, particular person cells can fluctuate extensively from one another. Internally, most cancers cells can develop distinctive DNA mutations and genomic modifications, doubtlessly resulting in drug resistance, metastasis, or relapse. Externally, the cells’ particular areas inside the tissue additionally matter, because the native construction of a tumor and its surrounding tissues can have an effect on cell state and drug permeability.

To measure each genetic and native components on the similar time, researchers from Harvard University’s Department of Stem Cell and Regenerative Biology (HSCRB) and the Broad Institute of MIT and Harvard developed a brand new strategy of spatially-resolved DNA sequencing, referred to as slide-DNA-seq. When additional mixed with spatially-resolved gene expression analysis, the know-how offers researchers a greater understanding of most cancers development and potential therapy.

The researchers’ findings are printed within the journal Nature.

Slide-DNA-seq analyzes slices of intact tissue, during which every cell stays in its authentic location—versus typical sequencing methods, the place cells are dissociated earlier than DNA extraction. The researchers used microbeads, every tagged with a novel spatial barcode and certain to specially-prepared glass slides, to seize DNA from the tissue.

“Each bead is about the size of a cell,” mentioned co-corresponding writer Fei Chen, who’s an assistant professor in HSCRB and a core institute member on the Broad Institute. “Together, they are like individual pixels on a camera which takes snapshots of genomic alterations within each cell in the tissue.”

After measuring genomic modifications, the researchers utilized a associated RNA-based Slide-seq methodology Chen and collaborators developed in 2019, which used gene expression profiles to determine and map the areas of cell varieties and subtypes inside a tissue slice.

“We can use the same barcoded beads to capture the transcriptome from each cell, and combine these two measurements into a multi-modal image,” Chen mentioned. In different phrases, the researchers can see modifications in each the cells’ DNA and gene expression inside the context of tissues.

The researchers utilized the method to a mouse mannequin of metastatic most cancers, in addition to a major tumor pattern from a affected person with colorectal most cancers. In every tissue, the researchers had been capable of determine subpopulations of cancer cells in distinct areas, corresponding with distinctive genomic evolutionary paths and gene expression states.

“We utilized this to DNA sequencing and cancer, that are vastly essential areas of medical analysis,” mentioned co-corresponding writer Jason Buenrostro, who’s a HSCRB assistant professor, an affiliate member of the Broad Institute, and co-director of the Broad’s Gene Regulation Observatory. “However, the technology also opens the door to more broadly measuring DNA molecules within tissues. As such, we imagine future approaches will use this work as a foundation to build tools that measure modifications to DNA as well, such as the epigenome.”