Project description:To identify and purify NEUROG2-expressing cells and trace their short-term lineage, we engineered two NEUROG2-mCherry knock-in human embryonic stem cell (hESC) lines. Transcriptomic profiling of NEUROG2:mCherry knock-in hESC-derived cerebral organoids revealed an enrichment of neurogenic, oligodendrocyte precursor cell and extracellular matrix-associated gene transcripts in mCherry-high cells. Conversely, only neurogenic gene transcripts were enriched in mCherry-high cells from Neurog2:mCherry knock-in mouse cortices.
Project description:Bulk ATAC-seq was performed on human, chimpanzee, bonobo, and macaque stem cell-derived cerebral organoids. ATAC-seq was performed on day 60 (2 months old) and day 120 (4 months old) cerebral organoids.
Project description:Pluripotent stem cells (PSC) can differentiate inot any cell type of an organism. Their remarkable capability of self-organization enables the formation of three-dimensional structures that resembles miniature organs, including cerebral organoids. These organoids can recreate early steps of the human cerebral cortex development, and show great potential for modeling human diseases, particularly for those with a developmental component. This data evidences stem cell-derived cerebral organoids as a key model to study brain development and neurodevelopmental, neurodegenerative and neuropsychiatric diseases.
Project description:The organoids heterogenously expressed mCherry by the lentivirus transduction were dissociated into single cells. A single mCherry- positive and -negative cell were collected and grown up to the organoids, respectivery. The difference of the gene expression profile between mCherry- positive and -negative organoids was assessd by maicroarray.
Project description:Humans exemplify gyrencephalic species with folded cerebral cortices, contrasting with lissencephalic mammals such as mice. Here we investigated how proneural genes Neurog2 and Ascl1 control cortical folding by regulating neurogenic patterns. Cortical neural progenitor cells (NPCs) stratify into four pools (proneural negative, Neurog2+, Ascl1+, double+) that are distributed evenly in mouse cortices and modular in gyrencephalic macaque cortices and pseudo-folded human cerebral organoids. Each pool has distinct developmental potentials, transcriptomes, epigenomes, and gene regulatory networks. Neurog2-Ascl1 form a bistable toggle switch double+ NPCs to prevent lineage commitment observed in single+ NPCs. Neurog2 and Ascl1 act redundantly to control neurogenic timing, with NPCs precociously depleted in Neurog2-/-;Ascl1-/- cortices. Finally, selective killing of Neurog2/Ascl1 double+ NPCs using Neurog2/Ascl1 split-Cre;Rosa-DTA transgenics breaks neurogenic symmetry in mice by locally disrupting Notch signaling, leading to cortical folding. Our findings suggest that Neurog2/Ascl1 double+ NPCs are Notch-ligand expressing ‘niche’ cells that regulate neurogenic continuity and cortical gyrification.
Project description:To characterize cerebral organoids generated using STEMdiff Dorsal Forebrain Organoid Differentiation Kit were flash frozen on Day 30, we performed single cell RNA sequencing
Project description:Single cell ATAC-seq (scATAC-seq) was performed on bonobo induced pluripotent stem cells (iPSC) derived cerebral organoids. scATAC-seq was performed on day 60 (2 months old cerebral organoid) and day 120 (4 months old cerebral organoid).
Project description:Single cell ATAC-seq (scATAC-seq) was performed on macaque embryonic stem cell-derived cerebral organoids. scATAC-seq was performed on day 60 (2 months old cerebral organoid).
Project description:Single cell ATAC-seq (scATAC-seq) was performed at various stages of differentiation of human pluripotent stem cells to 4 month old cerebral organoids. scATAC-seq was performed on the following days of differentiation: day 0 (pluripotent stem cell), day 4 (embryoid body), day 10 (neuroectoderm), day 15 (neuroepithelium), day 30 (1 month old cerebral organoid), day 60 (2 months old cerebral organoid), and day 120 (4 months old cerebral organoid).