02763nas a2200409   4500000000100000000000100001008004100002260001200043653002400055653003100079100001200110700001500122700002000137700001800157700001600175700002700191700001700218700002000235700001700255700001600272700002900288700001300317700002500330700001400355700002400369700001800393700002600411700001300437700001600450700002500466245007000491856005500561300001200616490000800628520170300636022001402339       2025                            d  c2025-1110aCell type diversity10aDevelopmental neurogenesis1 aLi Wang1 aCheng Wang1 aJuan A. Moriano1 aSongcang Chen1 aGuolong Zuo1 aArantxa Cebrián-Silla1 aShaobo Zhang1 aTanzila Mukhtar1 aShaohui Wang1 aMengyi Song1 aLilian Gomes de Oliveira1 aQiuli Bi1 aJonathan J. Augustin1 aXinxin Ge1 aMercedes F. Paredes1 aEric J. Huang1 aArturo Alvarez-Buylla1 aXin Duan1 aJingjing Li1 aArnold R. Kriegstein00aMolecular and cellular dynamics of the developing human neocortex  uhttps://www.nature.com/articles/s41586-024-08351-7  a169-1780 v6473 aThe development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation1. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalogue cell-type-specific, age-specific and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the neurogenesis-to-gliogenesis transition. We identified a tripotential intermediate progenitor subtype—tripotential intermediate progenitor cells (Tri-IPCs)—that is responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes. Notably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale genome-wide association study data, we created a disease-risk map highlighting enriched risk associated with autism spectrum disorder in second-trimester intratelencephalic neurons. Our study sheds light on the molecular and cellular dynamics of the developing human neocortex.  a1476-4687