Dual Chromatin Repressors Regulate Hippocampal Development

The cell fate transition from radial glial-like (RGL) cells to neurons and astrocytes is crucial for development and pathological conditions. Two chromatin repressors- the enhancer of zeste homolog 2 and suppressor of variegation 4-20 homolog, are highly associated with RGL cells in the hippocampus, implicating hippocampal cell fate commitment underlying these epigenetic regulations. Using a double knock-out mouse model, we demonstrated that loss of both chromatin repressors in the RGL population leads to deficits in hippocampal development. At the molecular level, single nuclei RNA-Seq revealed differential gene expression and provided mechanistic insight that dual chromatin repressors are critical for the maintenance of cycling cells in the dentate gyrus as well as the balance of cell trajectories between neuronal and astroglial lineages. Overall design: Linked flow cytometry and single-nuclei RNAseq datasets from wild-type and double knock-out of Ezh2 and Suv4-20h mice brains