KMT2D is essential for cerebellar granule cell differentiation

The cerebellum contains 62%-73% of the total number of neurons in the mouse brain. Granule cells (GCs) constitute the vast majority of cerebellar neurons. Single cell RNA-seq analyses showed that Atoh1-Cre-mediated knockout (KO) of the Kmt2d gene encoding the lysine methyltransferase KMT2D (MLL4 and a COMPASS-like enzyme) in the cerebellar GC lineage in mice inhibited cerebellar GC differentiation and downregulated neuron differentiation expression programs. In addition, Kmt2d KO inhibited the transition of GC progenitors to GCs while having a cell-non-autonomous impact on other cerebellar cells. Overall design: To examine the effect of Kmt2d KO on cerebellar cells at the single-cell level, cells were isolated from Kmt2d fl/fl (= WT) and Atoh1-Cre Kmt2d fl/fl (= Kmt2d KO) P5 cerebella (female and male). Then, the scRNA-seq (~300 millions read per sample) were performed to obtain single-cell transcriptomes.