Repurposing of a gill gene regulatory program for outer ear evolution.

How novel structures emerge during evolution has long fascinated biologists. A dramatic example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones. In contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, in part because it is supported by non-mineralized elastic cartilage rarely recovered in fossils.

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.

Implementation and validation of single-cell genomics experiments in neuroscience.

Single-cell or single-nucleus transcriptomics is a powerful tool for identifying cell types and cell states. However, hypotheses derived from these assays, including gene expression information, require validation, and their functional relevance needs to be established. The choice of validation depends on numerous factors.

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.

In Vivo CRISPR Screening Reveals CHD7 as a Positive Regulator of Short-lived Effector Cells.

CD8+ T cells differentiate into two subpopulations in response to acute viral infection: memory precursor effector cells (MPECs) and short-lived effector cells (SLECs). MPECs and SLECs are epigenetically distinct; however, the epigenetic regulators required for formation of these subpopulations are mostly unknown. In this study, we performed an in vivo CRISPR screen in murine naive CD8+ T cells to identify the epigenetic regulators required for MPEC and SLEC formation, using the acute lymphocytic choriomeningitis virus Armstrong infection model.

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.

A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells.

Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells.

Convergent evolution of plant prickles by repeated gene co-option over deep time.

An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. In this work, we genetically dissected repeated origins and losses of prickles-sharp epidermal projections-that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genus .

Associations of CD4 Cell Count Measures With Infection-Related and Infection-Unrelated Cancer Risk Among People With HIV.

Background: People with HIV are at higher risk of infection-related cancers than the general population, which could be due, in part, to immune dysfunction. Our objective was to examine associations between 4 CD4 count measures as indicators of immune function and infection-related and infection-unrelated cancer risk.

Setting: We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada.

Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response.

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.

Projected estimates of cancer in Canada in 2024.

Background: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined.

Methods: We obtained data on new cancer cases (i.

Sensory neurons: An integrated component of innate immunity.

The sensory nervous system possesses the ability to integrate exogenous threats and endogenous signals to mediate downstream effector functions. Sensory neurons have been shown to activate or suppress host defense and immunity against pathogens, depending on the tissue and disease state. Through this lens, pro- and anti-inflammatory neuroimmune effector functions can be interpreted as evolutionary adaptations by host or pathogen.

Identification of multiple transcription factor genes potentially involved in the development of electrosensory mechanosensory lateral line organs.

In electroreceptive jawed vertebrates, embryonic lateral line placodes give rise to electrosensory ampullary organs as well as mechanosensory neuromasts. Previous reports of shared gene expression suggest that conserved mechanisms underlie electroreceptor and mechanosensory hair cell development and that electroreceptors evolved as a transcriptionally related "sister cell type" to hair cells. We previously identified only one transcription factor gene, , as ampullary organ-restricted in the developing lateral line system of a chondrostean ray-finned fish, the Mississippi paddlefish ().

The origins of gas exchange and ion regulation in fish gills: evidence from structure and function.

Gill function in gas exchange and ion regulation has played key roles in the evolution of fishes. In this review, we summarize data from the fields of palaeontology, developmental biology and comparative physiology for when and how the gills first acquired these functions. Data from across disciplines strongly supports a stem vertebrate origin for gas exchange structures and function at the gills with the emergence of larger, more active fishes.

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.