To understand transcriptional regulation in human MGE and cortex development, we focused on alterations in chromatin accessibility, a key epigenetic regulation of transcription in the brain. We profiled genome-wide chromatin accessibility of 72-day old hMGEOs, hCOs, and their parental ESCs by Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq). Differentially open chromatin regions (dOCRs) were identified between organoids and ESCs. Over 10,000 increased and over 20,000 decreased dOCRs were found after differentiation from ESCs to either hMGEOs or hCOs (Figure S2). Open chromatin was observed preferentially for genes activated during organoid development (p<2.2e-16), with closed chromatin in suppressed genes (p<3.32e-5) (left and right panel in Figure 4E). Genes involved in dendrite development commonly displayed open chromatin conformation in both hMGEOs and hCOs (Figure 4F). Meanwhile, hMGEOs and hCOs showed subsets of dOCRs enriched for genes specifically expressed in hMGEOs (p=2.02e-3) or hCOs (p=4.44e-4) (bottom panel in Figure 4E). Especially, chromatin regions related to oligodendrocyte genes were specifically open in hMGEOs, and those involved in endothelium development were specifically open in hCOs. Importantly, open chromatin regions unique to hMGEOs were
