Biology subjects

Kuan, S.

Publications and source records attributed to Kuan, S..

2 recordsLinked to original sources

bioRxiv2020

An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

The mammalian cerebrum performs high level sensory, motor control and cognitive functions through highly specialized cortical networks and subcortical nuclei. Recent surveys of mouse and human brains with single cell transcriptomics1-3 and high-throughput imaging technologies4,5 have uncovered hundreds of neuronal cell types and a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each brain cell type have yet to be elucidated. Here, we probe the accessible chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types. We link a significant fraction of them to putative target genes expressed in diverse cerebral cell types and uncover transcriptional regulators involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of non-coding risk variants associated with various neurological disease and traits in humans. To facilitate the dissemination of information, we have set up a web portal (http://catlas.org/mousebrain).

neuroscience↗

bioRxiv2017

Single nucleus analysis of the chromatin landscape in mouse forebrain development

Genome-wide analysis of chromatin accessibility in primary tissues has uncovered millions of candidate regulatory sequences in the human and mouse genomes1-4. However, the heterogeneity of biological samples used in previous studies has prevented a precise understanding of the dynamic chromatin landscape in specific cell types. Here, we show that analysis of the transposase-accessible-chromatin in single nuclei isolated from frozen tissue samples can resolve cellular heterogeneity and delineate transcriptional regulatory sequences in the constituent cell types. Our strategy is based on a combinatorial barcoding assisted single cell assay for transposase-accessible chromatin5 and is optimized for nuclei from flash-frozen primary tissue samples (snATAC-seq). We used this method to examine the mouse forebrain at seven development stages and in adults. From snATAC-seq profiles of more than 15,000 high quality nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell-types in foetal and adult forebrains. We further define cell-type specific cis regulatory sequences and infer potential master transcriptional regulators of each cell population. Our results demonstrate the feasibility of a general approach for identifying cell-type-specific cis regulatory sequences in heterogeneous tissue samples, and provide a rich resource for understanding forebrain development in mammals.

genomics↗