Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

Repeated evolution of eye loss in Mexican cavefish: Evidence of similar developmental mechanisms in independently evolved populations.

Evolution in similar environments often leads to convergence of behavioral and anatomical traits. A classic example of convergent trait evolution is the reduced traits that characterize many cave animals: reduction or loss of pigmentation and eyes. While these traits have evolved many times, relatively little is known about whether these traits repeatedly evolve through the same or different molecular and developmental mechanisms.

Molecular signatures of retinal ganglion cells revealed through single cell profiling.

Retinal ganglion cells can be classified into more than 40 distinct subtypes, whether by functional classification or transcriptomics. The examination of these subtypes in relation to their physiology, projection patterns, and circuitry would be greatly facilitated through the identification of specific molecular identifiers for the generation of transgenic mice. Advances in single cell transcriptomic profiling have enabled the identification of molecular signatures for cellular subtypes that are only rarely found.

The Trim family of genes and the retina: Expression and functional characterization.

To better understand the mechanisms that govern the development of retinal neurons, it is critical to gain additional insight into the specific intrinsic factors that control cell fate decisions and neuronal maturation. In the developing mouse retina, Atoh7, a highly conserved transcription factor, is essential for retinal ganglion cell development. Moreover, Atoh7 expression in the developing retina occurs during a critical time period when progenitor cells are in the process of making cell fate decisions.

ALS-associated genes display CNS expression in the developing zebrafish.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle atrophy resulting from the deterioration of motor neurons in the central nervous system (CNS). Recent genome-wide association studies have revealed several genes linked to ALS, further demonstrating the complexity of the disease. The zebrafish (Danio rerio) is an attractive model organism to study the function of the rapidly expanding number of ALS-associated genes, in part, due to the development of genome editing techniques that have facilitated specific gene targeting.

Single-cell RNA-Seq of Defined Subsets of Retinal Ganglion Cells.

The discovery of cell type-specific markers can provide insight into cellular function and the origins of cellular heterogeneity. With a recent push for the improved understanding of neuronal diversity, it is important to identify genes whose expression defines various subpopulations of cells. The retina serves as an excellent model for the study of central nervous system diversity, as it is composed of multiple major cell types.

Single cell transcriptome profiling of developing chick retinal cells.

The vertebrate retina is a specialized photosensitive tissue comprised of six neuronal and one glial cell types, each of which develops in prescribed proportions at overlapping timepoints from a common progenitor pool. While each of these cells has a specific function contributing to proper vision in the mature animal, their differential representation in the retina as well as the presence of distinctive cellular subtypes makes identifying the transcriptomic signatures that lead to each retinal cell's fate determination and development challenging. We have analyzed transcriptomes from individual cells isolated from the chick retina throughout retinogenesis.

Complementary feature selection from alternative splicing events and gene expression for phenotype prediction.

Motivation: A central task of bioinformatics is to develop sensitive and specific means of providing medical prognoses from biomarker patterns. Common methods to predict phenotypes in RNA-Seq datasets utilize machine learning algorithms trained via gene expression. Isoforms, however, generated from alternative splicing, may provide a novel and complementary set of transcripts for phenotype prediction.

Disentangling neural cell diversity using single-cell transcriptomics.

Cellular specialization is particularly prominent in mammalian nervous systems, which are composed of millions to billions of neurons that appear in thousands of different 'flavors' and contribute to a variety of functions. Even in a single brain region, individual neurons differ greatly in their morphology, connectivity and electrophysiological properties. Systematic classification of all mammalian neurons is a key goal towards deconstructing the nervous system into its basic components.

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo.

Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma.

Expression Profiling of Developing Zebrafish Retinal Cells.

During retinal development, a variety of different types of neurons are produced. Understanding how each of these types of retinal nerve cells is generated is important from a developmental biology perspective. It is equally important if one is interested in how to regenerate cells after an injury or a disease.

Polo-Like Kinase 3 Appears Dispensable for Normal Retinal Development Despite Robust Embryonic Expression.

During retinogenesis seven different cell types are generated in distinct yet overlapping timepoints from a population of retinal progenitor cells. Previously, we performed single cell transcriptome analyses of retinal progenitor cells to identify candidate genes that may play roles in the generation of early-born retinal neurons. Based on its expression pattern in subsets of early retinal cells, polo-like kinase 3 (Plk3) was identified as one such candidate gene.

Transcriptomic analyses of Onecut1 and Onecut2 deficient retinas.

In this article, we further explore the data generated for the research article "Onecut1 and Onecut2 play critical roles in the development of the mouse retina". To better understand the functionality of the Onecut family of transcription factors in retinogenesis, we investigated the retinal transcriptomes of developing and mature mice to identify genes with differential expression. This data article reports the full transcriptomes resulting from these experiments and provides tables detailing the differentially expressed genes between wildtype and Onecut1 or 2 deficient retinas.

Onecut1 and Onecut2 play critical roles in the development of the mouse retina.

The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development.

Loss of gq/11 genes does not abolish melanopsin phototransduction.

In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity.

Making of a retinal cell: insights into retinal cell-fate determination.

Understanding the process by which an uncommitted dividing cell produces particular specialized cells within a tissue remains a fundamental question in developmental biology. Many tissues are well suited for cell-fate studies, but perhaps none more so than the developing retina. Traditionally, experiments using the retina have been designed to elucidate the influence that individual environmental signals or transcription factors can have on cell-fate decisions.

Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.

Cone photoreceptors carry out phototransduction in daylight conditions and provide the critical first step in color vision. Despite their importance, little is known about the developmental mechanisms involved in their generation, particularly how they are determined relative to rod photoreceptors, the cells that initiate vision in dim light. Here, we report the identification of a cis-regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an early cone marker.

Analysis of gene expression in wild-type and Notch1 mutant retinal cells by single cell profiling.

Background: The vertebrate retina comprises sensory neurons, the photoreceptors, as well as many other types of neurons and one type of glial cell. These cells are generated by multipotent and restricted retinal progenitor cells (RPCs), which express Notch1. Loss of Notch1 in RPCs late during retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia.

Plasma-seq: a novel strategy for metastatic prostate cancer analysis.

Unlabelled: Personalized genomics will only be useful for monitoring the prognosis of patients with cancer when it becomes much more cost-effective and quicker to apply. A recent study brings this closer to reality with the development of plasma-seq, a rapid, low-cost method that sequences the circulating DNA present in the peripheral blood of patients with cancer. The power of this technique is demonstrated with the examination of tumor genomes from patients with prostate cancer.

Single-cell profiling of developing and mature retinal neurons.

Highly specialized, but exceedingly small populations of cells play important roles in many tissues. The identification of cell-type specific markers and gene expression programs for extremely rare cell subsets has been a challenge using standard whole-tissue approaches. Gene expression profiling of individual cells allows for unprecedented access to cell types that comprise only a small percentage of the total tissue(1-7).

Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates.

Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression-profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix transcription factor, Olig2. The embryonic Olig2(+) RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time.

Development and diversification of retinal amacrine interneurons at single cell resolution.

The vertebrate retina uses diverse neuronal cell types arrayed into complex neural circuits to extract, process, and relay information from the visual scene to the higher order processing centers of the brain. Amacrine cells, a class of interneurons, are thought to mediate much of the processing of the visual signal that occurs within the retina. Although amacrine cells display extensive morphological diversity, the molecular nature of this diversity is largely unknown.

Identification of genes expressed preferentially in the developing peripheral margin of the optic cup.

Specification of the peripheral optic cup by Wnt signaling is critical for formation of the ciliary body/iris. Identification of marker genes for this region during development provides a starting point for functional analyses. During transcriptional profiling of single cells from the developing eye, two cells were identified that expressed genes not found in most other single cell profiles.