Nature Genetics: Single-cell multi-omics technology directly hits the powerful recovery ability of brain tumors

A team led by researchers from Weill Cornell Medical School, New York Genome Center, Harvard Medical School, Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Broad Institute Thousands of individual cells have been analyzed in unprecedented detail

The researchers reported in the journal Nature Genetics that they used advanced technology to record gene mutations, gene activity, and DNA methylation in individual tumor cells collected from patients with glioma (the most common type of brain cancer).

Combining their single-cell method and molecular clock technology, the researchers created an "ancestral tree" for the sampled tumor cells, describing the history of their state changes

"It's like having a time machine where we can extract samples from a patient's tumor and infer many details about how the tumor develops," said co-senior author Dr.

"We have been able to observe the fundamental impact on how we should consider treating glioma," said the second author of the article, Dr.

Traditionally, tumor cells are characterized by a large number, rather than a single one, and by relatively simple means, such as the type of their cell source and the receptors carried on their surface

In this new study, they used a three-tiered method—not only recording gene sequence and gene transcription information, but also recording “epigenetic” transcription—controlling methylation marks on DNA—this This is the first time it has been recorded on a single tumor cell directly from a patient

They found that the cells in the two cancers tend to be in one of four different states, from stem cell-like states to more mature brain cells

Although what the researchers captured is basically a snapshot of the state of tumor cells, they also designed a molecular clock method that calculates the lineage tree of each cell and describes it based on the random changes in DNA methylation that occur naturally over time.

These lineage trees show that compared with cells from low-grade gliomas, glioblastoma cells have a high degree of "plasticity", making them relatively easy to switch back and forth between the stem-like state and the mature state

"The very plastic cell structure of idh wild-type glioblastoma may allow it to survive stem cell killing by regenerating those cells from a more mature cell pool," said a postdoctoral researcher and co-author of Landau's laboratory.

Collectively, these findings provide rich insights on the dynamics of gliomas, which should help to develop better methods for detection, staging, monitoring, and treatment of gliomas

The researchers now plan to use their single-cell multi-omics approach to study the response of gliomas to different treatments