Project description:Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile the activity of human gene regulatory elements in diverse cell types and tissues in the human body, we applied single cell chromatin accessibility assays to 25 distinct human tissue types from multiple donors. The resulting chromatin maps comprising ~500,000 nuclei revealed the status of open chromatin for over 750,000 candidate cis-regulatory elements (cCREs) in 54 distinct cell types. We further delineated cell type-specific and tissue-context dependent gene regulatory programs, and developmental stage specificity by comparing with a recent human fetal chromatin accessibility atlas. We finally used these chromatin maps to interpret the noncoding variants associated with complex human traits and diseases. This rich resource provides a foundation for the analysis of gene regulatory programs in human cell types across tissues and organ systems.
Project description:Recent surveys of mouse organogenesis cell atlas (MOCA) with single cell transcriptomics have uncovered hundreds of cell types, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each cell type have yet to be elucidated. We applied a four-level combinatorial indexing assay, SPATAC-seq, to profile the chromatin accessibility in >350,000 cells derived from 13 embryos staged between embryonic day (E) 10.5 and 13.5 in a single experiment. The resulting map revealed the status of open chromatin for 844,817 candidate cis-regulatory elements (cCREs) in 33 main cell types and 296 subtypes. By integrating this accessible chromatin atlas with scRNA data of MOCA, we characterized the gene regulatory sequences and transcription factors associated with cell fate commitment, such as unreported role of Nr5a2 and Gata6 in gastrointestinal tract. Finaly, we integrated this atlas with previous scATAC-seq data from mouse embryos at E8.25 and 13 adult mouse tissues to dissect life stage specific gene regulatory programs across different cell types. This rich resource and comprerhensive analysis provide a foundation for expolring gene regulators in mammalian cell differentiation.
Project description:The majority of common genetic risk variants associated with neuropsychiatric disease are non-coding and are thought to exert their effects by disrupting the function of cis regulatory elements (CREs), including promoters and enhancers. Within each cell, chromatin is arranged in specific patterns to expose the repertoire of CREs required for optimal spatiotemporal regulation of gene expression. To further our understanding of the complex mechanisms that modulate transcription in the brain, we utilized frozen postmortem samples to generate the largest human brain and cell type-specific open chromatin dataset to date. Using the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq), we created maps of chromatin accessibility in 2 cell types (neurons and non-neurons) across 14 distinct brain regions of 5 individuals. Chromatin structure varies markedly by cell type, with neuronal chromatin displaying higher regional variability than that of non-neurons. Among our findings is an open chromatin region (OCR) specific to neurons of the striatum. When placed in the mouse, a human sequence derived from this OCR recapitulates the cell-type and regional expression pattern predicted by our ATAC-seq experiments. Furthermore, differentially accessible chromatin overlaps with the genetic architecture of neuropsychiatric traits and identifies differences in molecular pathways and biological functions. By leveraging transcription factor binding analysis, we identify protein coding and long noncoding RNAs (lncRNAs) with cell-type and brain region specificity. Our data provides a valuable resource to the research community and we provide this human brain chromatin accessibility atlas as an online database “Brain Open Chromatin Atlas (BOCA)” to facilitate interpretation.
Project description:A tissue atlas covering 25 mouse organs generated using an ECM-optimized 3-step extraction method and acquired using a Fusion Lumos MS system.
Project description:Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile the activity of gene regulatory elements in diverse cell types and tissues in the human body, we applied single-cell chromatin accessibility assays to 30 adult human tissue types from multiple donors. We integrated these datasets with single-cell chromatin accessibility data from 15 fetal tissue types to reveal the status of open chromatin for approximately 1.2 million candidate cis-regulatory elements (cCREs) in 222 distinct cell types comprised of >1.3 million nuclei. We used these chromatin accessibility maps to delineate cell type-specificity of fetal and adult human cCREs and to systematically interpret the noncoding variants associated with complex human traits and diseases. This rich resource provides a foundation for the analysis of gene regulatory programs in human cell types across tissues, life stages, and organ systems.
Project description:Single-cell technologies have ushered in a new era for Drosophila research, allowing researchers to obtain transcriptomes for all stable cell types and dynamic cell states. Here we present the first release of the adult Fly Cell Atlas (FCA), which includes 580k cells from 15 individually dissected sexed tissues, as well as from the entire head and body. We annotated more than 250 distinct cell types across all tissues. Few cell types were uniquely detected in the entire head and body samples, suggesting high cell-type saturation. We provide an in-depth analysis of gene signatures and transcription factor combinations, as well as sexual dimorphism, across the whole animal. Finally, we studied cell type lineages that are shared between tissues, such as blood cells and muscle cells, allowing the retrieval of rare cell types and tissue- specific subtypes. This atlas provides a valuable resource for the entire Drosophila community as a reference to study genetic perturbations and disease models at single-cell resolution.
Project description:Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated through examination of the chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1482 distinct brain cell populations, adding over 446,000 new cCREs to the most recent such annotation in the mouse genome. Raw fastq files are demultiplexed. Out of 234 samples, fastq files for 6 samples are available in NCBI under the accession number GSE126724 (CEMBA180308_3B, CEMBA180312_3B, CEMBA180226_1A, CEMBA180227_1A, CEMBA180305_2B, CEMBA180306_2B). Processed data are SnapATAC2 (<= 2.4.0) h5ad files per sample, with raw fragments and 500-bp bmat. NOTE: due to the break changes in SnapATAC2 >= 2.5.0, the data can not be handled rightly in SnapATAC2 >= 2.5.0.