Cells of one organism carry nearly the same set of DNA, but they work differently. This is especially evident in the brain: its different regions activate different genes and are responsible for different tasks. A key role here is played by chemical modifications of DNA and RNA — peculiar marks that influence how a cell reads genetic information.
The problem is that tissue has long been often analyzed as a single sample. This approach is convenient, but it erases important differences between adjacent areas.
Imagine an ancient archive where each scroll is marked with symbols visible only under special light. These signs hint at how to read the text. DREAMS works roughly like this: it highlights molecular features of cells and shows where exactly in the tissue signals related to reading genetic information are distributed. This is not just a new technical tool — it can help study epigenetic diseases in a new way.
The DREAMS method — DNA RNA Elements Areal Mass Spectrometry — is presented in the journal Nature Cell Biology. It adds a spatial dimension to molecular data. It is based on mass spectrometry imaging: a stream of charged microdroplets extracts molecules from the surface of a thin tissue section, after which the instrument determines their composition.
Researchers are interested in free modified nucleosides — products of DNA and RNA breakdown and renewal. Their distribution can indirectly indicate the state of corresponding modifications. However, DREAMS does not show the mark directly on a specific site of the molecule and does not replace sequencing. Its strength lies elsewhere: the method allows quickly finding areas with an unusual molecular profile and selecting them for more detailed analysis.
When DREAMS was applied to the mouse brain, it revealed noticeable heterogeneity. Different brain regions contained different sets of modified nucleosides, including 5-methylcytosine and rarer compounds. As a result, the averaged picture of the whole tissue split into several independent molecular landscapes.
Particularly interesting data were obtained in animals with impaired function of TET family enzymes. These enzymes are involved in the conversion of modified forms of cytosine and help regulate the epigenetic state of DNA. However, DREAMS showed changes not only in DNA modifications but also in N¹-methyladenosine (m¹A) — a compound mainly associated with RNA.
Changes in m¹A levels were accompanied by changes in the transcriptome. This indicates a possible link between processes dependent on TET1 and RNA regulation. In other words, the boundary between epigenomics and epitranscriptomics may not be as clear as commonly thought.
But it is too early to draw broad conclusions. The results do not prove that TET1 universally regulates RNA modifications. The study was mainly conducted on mouse tissues, and DREAMS signals themselves do not show causal relationships. There are also technical limitations: molecules with similar properties can be difficult to distinguish, and rare modifications may fall below the detection threshold. Therefore, the obtained data need to be confirmed by sequencing and other methods.
DREAMS will probably be most useful in combination with transcriptomics, cell type mapping, and other spatial biology technologies. Such an integrated approach will allow linking molecular changes not just to an organ as a whole, but to a specific tissue region and its cellular environment.
DREAMS reflects the general turn of modern biology — from averaged indicators to detailed spatial maps. Now it is important to know not only what changed in DNA, epigenome, or RNA, but also where exactly it happened. The method clearly shows: even one tissue can consist of many different molecular landscapes that completely disappear when analyzing an averaged sample.
