Donated Tissue is an Informative Tool in Medical Research

Among the many methods scientists use to understand human diseases, donated patient tissue is a uniquely precious tool. A recent study published this month in Nature Genetics investigated the heterogeneity of cell types and gene expression in DIPG/DMG patient tissue possessing the characteristic H3K27M histone mutation.

Dr. Mariella Filbin’s team, in collaboration with Dr. Mats Nilsson in Stockholm and Dr. Michelle Monje at Stanford (a GFAC Center of Excellence), utilized patient tissue donated across several years to analyze the cellular composition of these aggressive pediatric tumors. Previous research has suggested these tumors arise not from neurons, but from cells resembling oligodendrocyte precursor cells (OPCs). OPCs have many important functions in the brain throughout the lifespan. This study addresses ongoing questions in DMG research including: the gene expression profiles of these cancer cells, changes in expression between different brain region and patients, and the cellular arrangement of the tumor.

Researchers examined these cancer cell types by sequencing thousands of cells from 50 patient tumors, using methods to determine differentially expressed genes and common mutations amongst patients. They identified important differences across different tumor locations (pons vs thalamus) and at different ages. They found multiple sub-populations of malignant OPC-like cells consistent across their samples and patterns of cell types in pediatric patients vs adult patients. Additionally, tumors arising in the thalamus contained cells with a more differentiated gene profile compared with tumors in the pons. Scientists were also able to perform spatial transcriptomics experiments, a technique to visualize different tumor cell types in a piece of tumor tissue. Interestingly, they found niches of proliferative OPC-like tumor cells surrounded by other tumor cell types.

By studying patient tissue, we hope to gain insight as to how these tumors connect to the existing healthy tissue and respond to signals from nearby cells to encourage cancer growth. Finally, whether by sequencing or imaging via probes, this study illustrates the myriad of ways patient tissue can help answer scientific questions about the underlying biology of these cancers. These questions, being asked now and years in the future, will require the continued collaboration of scientists, physicians, and generous patient donors.

Link to read the full paper: https://www.nature.com/articles/s41588-022-01236-3

Paper Citation: Liu, I., Jiang, L., Samuelsson, E.R. et al. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nat Genet 54, 1881–1894 (2022). https://doi.org/10.1038/s41588-022-01236-3