Project description:Gene expression is finely regulated during development, and deregulation can lead to disease. In pediatric brain tumors (PBT), disruption of neurodevelopmental gene regulation programs are suspected to drive oncogenesis. However, the transcriptional landscape and genetic regulation processes of the healthy developing brain are not fully characterized, limiting our investigation of these tumors. We used single-cell RNA-sequencing to generate a transcriptomic atlas of >65,000 cells in the developing forebrain and pons in human and mouse, two regions where PBT commonly arise. We projected bulk RNA-seq profiles for a cohort of 198 PBT onto these cell types, followed by focused analysis of three PBT subtypes by single-cell profiling: WNT medulloblastoma, embryonal tumors with multilayered rosettes (ETMR), and atypical teratoid/rhabdoid tumors (ATRT). Altogether, we pinpoint stalled differentiation during developmental programs as a common etiological mechanism of PBT, providing a valuable resource to aid modeling and therapeutics.

2019-11-19 | GSE133531 | GEO

A High-Resolution Enhancer Atlas of the Developing Telencephalon

Project description:The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant‐acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web‐based enhancer atlas comprising over 33,000 sections. We show how this large collection of annotated telencephalon enhancers can be used to study the regulatory architecture of individual genes, to examine the sequence motif content of enhancers, and to drive targeted reporter or effector protein expression in experimental applications. Furthermore, we used epigenomic analysis of human and mouse cortex tissue to directly compare the genome‐wide enhancer architecture in these species. This atlas provides a primary resource for investigating gene regulatory mechanisms of telencephalon development and enables studies of the role of distant‐acting enhancers in neurodevelopmental disorders. Examination of p300 binding in mouse embryonic stage 11.5 forebrain, mouse postnatal (P0) cortex tissue and human fetal (gestational week 20) cortex

2013-01-29 | E-GEOD-42881 | biostudies-arrayexpress

3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis

Project description:Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may lead to the formation of new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.

2020-12-15 | GSE163177 | GEO

Single-cell transcriptome and 3D genome atlas of the developing mouse brain

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-07 | GSE162511 | GEO

Melanoma Brain Metastasis Atlas [SlideSeq]

Project description:Melanoma Brain Metastasis Atlas [SlideSeq]

| PRJNA823928 | ENA

Transcriptome analysis of 3D model of blood-brain barrier exposed to Borrelia garini

Project description:Using RNA sequencing to map differentially expressed genes in the 3D model of the blood-brain barrier ( composed of human brain endothelial cells, human astrocytes, and human pericytes) challenged with Borrelia garini .

2021-01-01 | E-MTAB-9753 | biostudies-arrayexpress

A single cell transcriptome atlas of the developing zebrafish hindbrain

Project description:A single cell transcriptome atlas of the developing zebrafish hindbrain

| PRJNA593433 | ENA