Single-cell transcriptomes have been used to identify tumour cells and their origins in paediatric brain cancers, providing a blueprint for one of the main zones where childhood cancers develop.

The study published in Nature Genetics gathered single-cell transcriptomes from over 65,000 cells that resulted in gene-expression profiles. After large scale data analysis, 191 distinct cell populations were identified and how each developed from one type to another. Transcriptomes are the sum total of all RNA molecules expressed from the genes in a sample – providing an insight into which genes are expressed, and in what quantities.

Brain cancer account for the greatest fatality rates of all childhood cancers. Little progress has been made in finding effective therapies for these cancers with a survival rate of less than two years. Accessibility during surgery to cancers growing in deeper areas of the brain, without damaging surrounding tissues, continues to limit development of effective therapies.

Most cells transition in an ordered manner from a progenitor to the mature and well-defined forms. However, cell lineages in the brain are much more complicated with multiple branching paths. Neuronal progenitor cells, for example, go on to form almost all of the neural cells in the central nervous system.

Mapping the genes that are expressed can be used to classify cells into their specific types. This is especially important considering that we don’t have a complete understanding of what constitutes normal brain development. This study aimed to create a blueprint for an area of the brain called the prenatal pons using large-scale single-cell transcriptomes. Many childhood brain cancers originate in this zone. The pons is part of the brainstem and involved in the control of breathing and communicating sensations.

During analysis of tumour cell transcriptomes, the researchers were able to identify cells that had stalled their development. These cells seem to ‘refuse’ to age. Early stalled cells go on to form malignancies and tumours instead of developing as normal.

“The challenge is now to identify how best to unlock these cells promoting their differentiation, and allowing for normal processes to take over” comments Dr Nada Jabado.

Ongoing research will be required to further elucidate the developmental pathways of cells implicated in tumour development, not limited to childhood brain cancers.

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