OUR FIRST ‘OMICS PAPER IN THE DEVELOPING HUMAN BRAIN

🧠 What can the epigenetic landscape of the developing human brain tell us about childhood brain cancer?

Our new publication is now out in The Cerebellum (Springer Nature)!

This work had contributions from Xinghan Sun, a PhD candidate in the Department of Medical Biophysics at the University of Toronto and Soumya Menon, an undergraduate co-op student from the University of Waterloo.

We used laser-capture microdissection and DNA methylation profiling to map the epigenetic landscape of the human cerebellar rhombic lip — a progenitor zone that is unusually expanded in humans compared to other species, and whose disruption is linked to medulloblastoma and cerebellar birth defects. To ground our findings in the broader regulatory landscape, we integrated our data with histone modification maps of the fetal human cerebellum, generously provided by Dr. Kimberly Aldinger and Birth Defect Research Laboratory at Seattle Children's Hospital.

Medulloblastoma is the most common malignant childhood brain tumor and remains poorly understood at the level of its non-coding genome. The rhombic lip gives rise to the very cells thought to be the origin of the most common medulloblastoma subgroups — so understanding what switches genes on and off in this region during development is an important piece of the puzzle.

We identified nearly 10,000 regions of the genome where DNA methylation differs across the rhombic lip, clustering in active enhancers, human accelerated regions, and — strikingly — in regions that are amplified or deleted in Group 3 and 4 medulloblastoma. We also predicted a gene regulatory network linking key transcription factors like ATOH1 and NEUROD1/2 to downstream genes relevant to both normal cerebellar development and medulloblastoma biology.

This work adds a new layer to our understanding of how the non-coding genome shapes cerebellar development and how its disruption may contribute to childhood brain cancer. Thank you to our collaborators, tissue donors, and everyone who provided feedback along the way. As always, community input is welcome — there is much more to explore here!

📖 [Read our work here.](https://link.springer.com/article/10.1007/s12311-026-02057-4)