Project description:During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using a dual reporter cell line to isolate neural progenitors and neurons from the telencephalic brain organoid tissue and performed cell type and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed temporal modules of gene expression during human corticogenesis, both at RNA and protein level. Our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for fidelity of cortical development.
Project description:The complexity of the mature adult brain is a result of both developmental processes and experience-dependent circuit formation. One way to look at the process of brain development is to examine gene expression changes, and previous studies have used microarrays to address this in a global manner. However, the transcriptome is more complex than gene expression levels alone, as both alternative splicing and RNA editing occur to generate a more diverse set of mature transcripts. The aim of the current study was to develop a high-resolution transcriptome dataset of mouse cortical development using RNA sequencing (RNA-Seq), thus assaying exon usage and RNA editing as well as overcoming some of the inherent limitations of microarrays. We found a large number of differentially expressed genes, but also altered splicing and RNA editing between embryonic and adult cerebral cortex. Each dataset was validated both technically and biologically, and in each case tested we found our RNA-Seq observations to have high predictive validity. We propose this dataset, and the accompanying analysis, to be a helpful resource in the understanding of changes in gene expression during development. Three young adult cerebral cortices four embryonic cerebral cortices
Project description:To determine the impact of Brap loss of function on cellular senescence in cerebral cortex, we performed gene expression profiling analysis of mice with Brap conditional deletions in neural progenitors, postnatal neurons, and vascular endothelium cells, respectively. To understand the premature death caused by Brap conditional deletions in neural progenitors or neurons, we also analyzed mice at two different ages.
Project description:The goals of this study are to compare transcriptome of Gad2 + inhibitory neurons, isolated from cerebral cortex of wild type and GTF2ird1-/- mice Wild type or GTF2ird1-/- were crossed with Gad2-Cre/Ai14, and total RNA was isolated from flow cytometry-sorted TdTomato positive cells
Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>
Project description:Objectives: The aim of this study was to reveal the transcriptomic profile of the cerebral cortex in traumatic brain injury (TBI) mice. Methods: A controlled cortical impact (CCI) device was used to establish a TBI model. The gene expression in the cerebral cortex was detected by whole-transcriptome sequencing (RNA-Seq).
Project description:The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge through the implementation of different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons, as they represent a relatively small proportion of all cortical cells, migrate tangentially from their embryonic origin to the cerebral cortex, and have a protracted development. Here we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells, the most diverse subclass of inhibitory neurons in the mouse cerebral cortex. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is further refined during early postanal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons. Thus, the diversification of SST+ inhibitory neurons involves a temporal cascade of unique molecular programs driving their divergent developmental trajectories.
Project description:During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. This process is faithfully recapitulated in brain organoids. By using telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons we generated a cell type and developmental stage-specific transcriptome dataset..