@article {65282, title = {A genetic, genomic, and computational resource for exploring neural circuit function.}, journal = {eLife}, volume = {9}, year = {2020}, month = {2020 Jan 15}, abstract = {

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of apparent co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.

}, issn = {2050-084X}, doi = {10.7554/eLife.50901}, author = {Davis, Fred P and Nern, Aljoscha and Picard, Serge and Reiser, Michael B and Rubin, Gerald M and Eddy, Sean R and Henry, Gilbert L} } @article {47412, title = {Epigenomic landscapes of retinal rods and cones.}, journal = {eLife}, volume = {5}, year = {2016}, month = {2016 Mar 07}, abstract = {

Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks, transcription factor binding, and DNA sequence motifs. Loss of NR2E3 in rods shifts their epigenomes to a more cone-like state. The data further reveal wide differences in DNA methylation between retinal photoreceptors and brain neurons. Surprisingly, we also find a substantial fraction of DNA hypo-methylated regions in adult rods that are not in active chromatin. Many of these regions exhibit hallmarks of regulatory regions that were active earlier in neuronal development, suggesting that these regions could remain undermethylated due to the highly compact chromatin in mature rods. This work defines the epigenomic landscapes of rods and cones, revealing features relevant to photoreceptor development and function.

}, issn = {2050-084X}, doi = {10.7554/eLife.11613}, author = {Mo, Alisa and Luo, Chongyuan and Davis, Fred P and Mukamel, Eran A and Henry, Gilbert L and Nery, Joseph R and Urich, Mark A and Picard, Serge and Lister, Ryan and Eddy, Sean R and Beer, Michael A and Ecker, Joseph R and Nathans, Jeremy} } @article {46852, title = {Epigenomic signatures of neuronal diversity in the mammalian brain.}, journal = {Neuron}, volume = {86}, year = {2015}, month = {2015 Jun 17}, pages = {1369-1384}, abstract = {

Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we developed the first\ affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We\ combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2015.05.018}, author = {Mo, Alisa and Mukamel, Eran A and Davis, Fred P and Luo, Chongyuan and Henry, Gilbert L and Picard, Serge and Urich, Mark A and Nery, Joseph R and Sejnowski, Terrence J and Lister, Ryan and Eddy, Sean R and Ecker, Joseph R and Nathans, Jeremy} } @article {6283, title = {Cell type-specific genomics of Drosophila neurons.}, journal = {Nucleic Acids Research}, volume = {40}, year = {2012}, month = {2012 Oct}, pages = {9691-704}, abstract = {

Many tools are available to analyse genomes but are often challenging to use in a cell type-specific context. We have developed a method similar to the isolation of nuclei tagged in a specific cell type (INTACT) technique [Deal,R.B. and Henikoff,S. (2010) A simple method for gene expression and chromatin profiling of individual cell types within a tissue. Dev. Cell, 18, 1030-1040; Steiner,F.A., Talbert,P.B., Kasinathan,S., Deal,R.B. and Henikoff,S. (2012) Cell-type-specific nuclei purification from whole animals for genome-wide expression and chromatin profiling. Genome Res., doi:10.1101/gr.131748.111], first developed in plants, for use in Drosophila neurons. We profile gene expression and histone modifications in Kenyon cells and octopaminergic neurons in the adult brain. In addition to recovering known gene expression differences, we also observe significant cell type-specific chromatin modifications. In particular, a small subset of differentially expressed genes exhibits a striking anti-correlation between repressive and activating histone modifications. These genes are enriched for transcription factors, recovering those known to regulate mushroom body identity and predicting analogous regulators of octopaminergic neurons. Our results suggest that applying INTACT to specific neuronal populations can illuminate the transcriptional regulatory networks that underlie neuronal cell identity.

}, keywords = {Animals, Cell Fractionation, Cell Nucleus, Chromatin, Drosophila, Gene Expression Profiling, Gene Silencing, Genomics, Histones, Luminescent Proteins, Neurons, Transcription Factors}, issn = {1362-4962}, doi = {10.1093/nar/gks671}, author = {Henry, Gilbert L and Davis, Fred P and Picard, Serge and Eddy, Sean R.} }