Delineating the gene regulatory programs underlying complex cell types is fundamental for understanding brain functions in health and disease. Here, we comprehensively examine human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in over 500,000 cells from 46 brain regions. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. With these resources, we developed scMCodes that reliably predict brain cell types using their methylation status at select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell type-specific gene regulation in the adult human brain.

Extensive studies of the reference plant Arabidopsis have enabled deep understandings of tissues throughout development, yet a census of cell types and states throughout development are lacking. Here, we present a single-nucleus transcriptome atlas of seed-to-seed development employing over 800,000 nuclei, encompassing a diverse set of tissues across ten developmental stages, with spatial transcriptomic validation of the dynamic seed and silique. Cross-organ analyses revealed transcriptional conservation of cell types throughout development but also heterogeneity within individual cell types influenced by organ-of-origin and developmental timing, including groups of transcription factors, suggesting gatekeeping by transcription factor activation. This atlas provides a resource for the study of cell type specification throughout the continuum of development, and a reference for stimulus- response and genetic perturbations at the single-cell resolution.

Simple, soil-free assays that can mimic drought conditions are incredibly useful for investigating plant stress responses. Due to their ease of use, the research community often relies on polyethylene glycol (PEG), mannitol and salt treatments to simulate drought conditions in the laboratory. However, while these types of osmotic stress can create phenotypes that resemble those of drought, it remains unclear how they compare at the molecular level. Here, using transcriptomics, we demonstrate that these assays are unable to replicate drought signaling responses in theArabidopsisroot. Indeed, we found a significant number of genes that were induced by drought were in fact repressed by such treatments. Since our results question the utility of PEG, mannitol and salt, we designed a new method for simulating drought. By simply adding less water to agar, our 'low-water agar' assay elicits gene expression responses that compare more favorably to drought stress. Furthermore, we show our approach can be leveraged as a high-throughput assay to investigate natural variation in drought responses.

Simple, soil-free assays that can mimic drought conditions are incredibly useful for investigating plant stress responses. Due to their ease of use, the research community often relies on polyethylene glycol (PEG), mannitol and salt treatments to simulate drought conditions in the laboratory. However, while these types of osmotic stress can create phenotypes that resemble those of drought, it remains unclear how they compare at the molecular level. Here, using transcriptomics, we demonstrate that these assays are unable to replicate drought signaling responses in the Arabidopsis root. Indeed, we found a significant number of genes that were induced by drought were in fact repressed by such treatments. Since our results question the utility of PEG, mannitol and salt, we designed a new method for simulating drought. By simply adding less water to agar, our ‘low-water agar’ assay elicits gene expression responses that compare more favorably to drought stress. Furthermore, we show our approach can be leveraged as a high-throughput assay to investigate natural variation in drought responses.