A new tool for tracking cells will provide more clues for early cancer diagnosis and treatment

In the microscopic world of life, each cell also has such a mysterious "family tree" that records the cell's "origin" and "inheritance". With division or differentiation, cells gradually form different types of cells and tissues. Some become nerve cells, building complex neural networks; some become muscle cells, providing power for body movement; and some differentiate into blood cells, responsible for transporting oxygen and nutrients...

This "family tree" of cells is called a cell lineage and is critical to understanding the developmental process of life and the origin and development of disease.

Recently, Wang Shouwen's team from the School of Life Sciences and West Lake Laboratory of West Lake University and Li Li's team have collaborated to develop a new computational tool for lineage tracing, MethylTree, in the field of single-cell lineage tracing. This tool can accurately track cell lineages in a multi-omics manner without gene editing, opening a new chapter in non-invasive lineage tracing and providing many possibilities for studying human tissue development, disease mechanisms and stem cell therapy.

Screenshot of the paper

Originating from microscope observations and records in the late 19th century, the study of cell lineage has been going on for a century. Many methods for studying cell lineage have been developed, but there are still some defects.

For example, some methods require editing of cellular DNA, which is not very mature either from an ethical or technical perspective, and is therefore not suitable for human research; and those methods that do not require direct editing of cells rely on rare somatic DNA mutations (the probability of mutation is extremely low, only 10-9 per nt/division), which not only have very high technical requirements but are also very expensive (approximately US$200 per cell).

Therefore, faced with these problems, the research team has been trying to develop a new efficient, accurate, multi-omics lineage tracing method.

The breakthrough point is a common epigenetic modification method on DNA, methylation. DNA methylation can regulate gene expression, sometimes shutting down the expression of certain genes, and sometimes inducing the reactivation and expression of genes.

Imagine that you have a very complex and informative book of life, which contains a vast amount of life information. Some chapters need to be read at specific times, while some chapters need to be ignored at specific times. Methylation is like a bookmark. They will not change the content of the book, but will tell you which chapters should be read now and which chapters can be temporarily ignored.

Cell lineages record the history of cell divisions within an individual

Therefore, the research team used the methylation characteristics of cells to successfully develop a new computational tool for lineage tracing, named MethylTree. Methyl means methylation, which means using the characteristics of cell methylation to track cell trees. MethylTree not only cleverly avoids the problem of missing values ​​and noise interference, but also successfully eliminates the impact of DNA methylation differences unique to different cell types.

At the same time, the team verified that the accuracy of MethylTree is close to 100% in multiple experimental systems such as the human hematopoietic system, early embryonic development, and cancer!

Figure 2: MethylTree successfully reconstructs the lineage of human umbilical cord blood. The clones in the MethylTree lineage heat map (right) are consistent with the clones defined by the lentivirus LARRY in the experiment (left).

What is the use of studying cell lineage?

By studying cell lineages, researchers can reveal the fate-determining mechanisms of different cell types and understand the development process of tissues and organs. They can also understand the lineage relationships of tumor cells, which may provide clues for early diagnosis and treatment of cancer. They can also understand how stem cells differentiate into specific types of cells, promoting the development of tissue engineering and organ regeneration technologies.

The research team has developed a tool, but their expectations are not limited to this tool. From the occurrence and development of diseases to the personalized optimization of treatments, they hope that more teams will join in and use this tool to unlock more mysteries in the process of cell development and differentiation.

(Source: Chao News, Westlake University)