Developmental landscape of human forebrain at a single-cell level identifies early waves of oligodendrogenesis. Developmental cell Oligodendrogenesis in the human central nervous system has been observed mainly at the second trimester of gestation, a much later developmental stage compared to oligodendrogenesis in mice. Here, we characterize the transcriptomic neural diversity in the human forebrain at post-conception weeks (PCW) 8-10. Using single-cell RNA sequencing, we find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level through the use of single-cell ATAC-seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of 50 key genes through the use of in situ sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mice and humans and describe regulatory mechanisms involved in human OPC specification. 10.1016/j.devcel.2022.04.016

RNA mA methylation participates in regulation of postnatal development of the mouse cerebellum. Genome biology BACKGROUND:N-methyladenosine (mA) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved in the regulation of memory formation and mammalian cortical neurogenesis. However, while it is now established that mA methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation. RESULTS:We identify widespread and dynamic RNA mA methylation in the developing mouse cerebellum and further uncover distinct features of continuous and temporal-specific mA methylation across the four postnatal developmental processes. Temporal-specific mA peaks from P7 to P60 exhibit remarkable changes in their distribution patterns along the mRNA transcripts. We also show spatiotemporal-specific expression of mA writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in the mouse cerebellum. Ectopic expression of METTL3 mediated by lentivirus infection leads to disorganized structure of both Purkinje and glial cells. In addition, under hypobaric hypoxia exposure, Alkbh5-deletion causes abnormal cell proliferation and differentiation in the cerebellum through disturbing the balance of RNA mA methylation in different cell fate determination genes. Notably, nuclear export of the hypermethylated RNAs is enhanced in the cerebellum of Alkbh5-deficient mice exposed to hypobaric hypoxia. CONCLUSIONS:Together, our findings provide strong evidence that RNA mA methylation is controlled in a precise spatiotemporal manner and participates in the regulation of postnatal development of the mouse cerebellum. 10.1186/s13059-018-1435-z