Examining the NEUROG2-lineage and associated-gene expression in human cortical organoids.

Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell (hESC)-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later.

RNA programmable cell targeting and manipulation with CellREADR.

Methods that provide specific, easy, and scalable experimental access to animal cell types and cell states will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell. The CellREADR RNA device consists of a 5' sensor region complementary to a cellular RNA and a 3' payload coding region; payload translation is gated by the removal of a STOP codon in the sensor region upon base pairing with the cognate cellular RNA through an ADAR-mediated A- to-I editing mechanism ubiquitous to metazoan cells.

Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue.

Human neural organoids offer an exciting opportunity for studying inaccessible human-specific brain development; however, it remains unclear how precisely organoids recapitulate fetal/primary tissue biology. We characterize field-wide replicability and biological fidelity through a meta-analysis of single-cell RNA-sequencing data for first and second trimester human primary brain (2.95 million cells, 51 data sets) and neural organoids (1.

Population variability in X-chromosome inactivation across 10 mammalian species.

One of the two X-chromosomes in female mammals is epigenetically silenced in embryonic stem cells by X-chromosome inactivation. This creates a mosaic of cells expressing either the maternal or the paternal X allele. The X-chromosome inactivation ratio, the proportion of inactivated parental alleles, varies widely among individuals, representing the largest instance of epigenetic variability within mammalian populations.

Cross-expression analysis reveals patterns of coordinated gene expression in spatial transcriptomics.

Spatial transcriptomics promises to transform our understanding of tissue biology by molecularly profiling individual cells . A fundamental question they allow us to ask is how nearby cells orchestrate their gene expression. To investigate this, we introduce cross-expression, a novel framework for discovering gene pairs that coordinate their expression across neighboring cells.

Coexpression enhances cross-species integration of single-cell RNA sequencing across diverse plant species.

Single-cell RNA sequencing is increasingly used to investigate cross-species differences driven by gene expression and cell-type composition in plants. However, the frequent expansion of plant gene families due to whole-genome duplications makes identification of one-to-one orthologues difficult, complicating integration. Here we demonstrate that coexpression can be used to trim many-to-many orthology families down to identify one-to-one gene pairs with proxy expression profiles, improving the performance of traditional integration methods and reducing barriers to integration across a diverse array of plant species.

Improving replicability in single-cell RNA-Seq cell type discovery with Dune.

Background: Single-cell transcriptome sequencing (scRNA-Seq) has allowed new types of investigations at unprecedented levels of resolution. Among the primary goals of scRNA-Seq is the classification of cells into distinct types. Many approaches build on existing clustering literature to develop tools specific to single-cell.

A Curated Compendium of Transcriptomic Data for the Exploration of Neocortical Development.

Vast quantities of multi-omic data have been produced to characterize the development and diversity of cell types in the cerebral cortex of humans and other mammals. To more fully harness the collective discovery potential of these data, we have assembled gene-level transcriptomic data from 188 published studies of neocortical development, including the transcriptomes of ~30 million single-cells, extensive spatial transcriptomic experiments and RNA sequencing of sorted cells and bulk tissues: nemoanalytics.org/landing/neocortex.

Defining Transcriptomic Heterogeneity between Left and Right Ventricle-Derived Cardiac Fibroblasts.

Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV.

Coexpression enhances cross-species integration of scRNA-seq across diverse plant species.

Single-cell RNA sequencing is increasingly used to investigate cross-species differences driven by gene expression and cell-type composition in plants. However, the frequent expansion of plant gene families due to whole genome duplications makes identification of one-to-one orthologs difficult, complicating integration. Here, we demonstrate that coexpression can be used to identify non-orthologous gene pairs with proxy expression profiles, improving the performance of traditional integration methods and reducing barriers to integration across a diverse array of plant species.

The transcriptional legacy of developmental stochasticity.

Genetic and environmental variation are key contributors during organism development, but the influence of minor perturbations or noise is difficult to assess. This study focuses on the stochastic variation in allele-specific expression that persists through cell divisions in the nine-banded armadillo (Dasypus novemcinctus). We investigated the blood transcriptome of five wild monozygotic quadruplets over time to explore the influence of developmental stochasticity on gene expression.

Population variability in X-chromosome inactivation across 9 mammalian species.

One of the two X chromosomes in female mammals is epigenetically silenced in embryonic stem cells by X chromosome inactivation (XCI). This creates a mosaic of cells expressing either the maternal or the paternal X allele. The XCI ratio, the proportion of inactivated parental alleles, varies widely among individuals, representing the largest instance of epigenetic variability within mammalian populations.

Comparative transcriptomics reveals human-specific cortical features.

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG.

A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization.

A pan-grass transcriptome reveals patterns of cellular divergence in crops.

Different plant species within the grasses were parallel targets of domestication, giving rise to crops with distinct evolutionary histories and traits. Key traits that distinguish these species are mediated by specialized cell types. Here we compare the transcriptomes of root cells in three grass species-Zea mays, Sorghum bicolor and Setaria viridis.

Preservation of co-expression defines the primary tissue fidelity of human neural organoids.

Human neural organoid models offer an exciting opportunity for studying often inaccessible human-specific brain development; however, it remains unclear how precisely organoids recapitulate fetal/primary tissue biology. Here, we characterize field-wide replicability and biological fidelity through a meta-analysis of single-cell RNA-sequencing data for first and second trimester human primary brain (2.95 million cells, 51 datasets) and neural organoids (1.

Learning single-cell chromatin accessibility profiles using meta-analytic marker genes.

Motivation: Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a valuable resource to learn cis-regulatory elements such as cell-type specific enhancers and transcription factor binding sites. However, cell-type identification of scATAC-seq data is known to be challenging due to the heterogeneity derived from different protocols and the high dropout rate.

Results: In this study, we perform a systematic comparison of seven scATAC-seq datasets of mouse brain to benchmark the efficacy of neuronal cell-type annotation from gene sets.

Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters.

Replication of the genome must be coordinated with gene transcription and cellular metabolism, especially following replication stress in the presence of limiting deoxyribonucleotides. The Rad53 (CHEK2 in mammals) checkpoint kinase plays a major role in cellular responses to DNA replication stress. Cell cycle regulated, genome-wide binding of Rad53 to chromatin was examined.