Publications and Posters

The authors graphed a novel application of summed gene expression differences onto data sets of known cell types, from diverse scRNA-Seq data sources. They found that distinct types and lineages were not clearly separated, and using their method and technical factors did not explain the discrepancy. They point to the arbitrariness of differing pipeline parameters not being designed to separate raw scRNA-seq data, and not producing the cell type based clusters per the expectations of Waddington’s epigenetic landscape model.

Inhibition of the C5aR1 receptor with PMX205 reduces plaque load and gliosis while improving short-term memory in Alzheimer's Disease (AD) mouse models. Using scRNA-Seq and snRNA-Seq, the authors found that PMX205 treatment enhanced cell growth and repair and decreased the inflammatory gene expression in microglia despite little alteration of the protein levels in reactive cells. The results highlight the attractiveness of a C5aR1 inhibition-based strategy.

Researchers used snRNA-Seq to compare gene expression in early and late-stage Alzheimer's Disease (AD) and AD in Down Syndrome (DS), bridging the gap between genetic mouse models and sporadic AD. The study revealed a complex interaction between the extra chr21 and the genome, identified shared and unique pathways between late-stage AD and AD in DS, and discovered sex-related expression differences in AD in DS, enhancing our understanding of factors influencing AD progression.

In a multisite study to test the reproducibility of human cortical organoids (hCO) differentiation protocols, scRNA-Seq was used to characterize cross-site similarities and differences. The results showed reproducible key features, such as cell type proportions and structure, including neuroepithelial budding and cortical wall-like organization, as well as some differences that limit the utility of hCO models. Understanding how stem cell states influence early hCO cell types could lead to more reliable hCO protocols for studying neurodevelopmental disorders.

Using snRNA-Seq on chicken embryos, researchers profiled gene expression and chromatin accessibility associated with the chicken ocular lens development. They found three distinct populations representing major cell states (epithelial, intermediate, and fiber cell) and established a continuous trajectory from epithelial to fiber cell differentiation. The study confirmed known pathways and cataract-linked genes while uncovering new factors involved in lens development, homeostasis, and pathology.

The authors compared various scRNA-Seq reagents. Parse WT v2 and 10x Flex were tested on fixed tumor nuclei. 10x Flex failed due to clogging. Parse data had more reads, genes, and fewer doublets than 10x fresh nuclei data. 10X data had high mitochondrial and ribosomal transcripts, but gene expression was concordant with Parse data. Parse WT v2 captured more biological variation and outperformed other assays.

Parse and 10X were compared using scRNA-seq on PBMC from 2 healthy donors. Parse demonstrated better data quality with lower multiplets rates but had lower cell recovery. Parse detected 1.2-fold more genes, had better clustering performance, and greater power in distinguishing cell types with specific gene signatures. Parse also excelled in detecting longer transcripts and rare cell types.

Alveolar epithelium regeneration and repair following injury is not completely understood. Evidence suggests that the Hippo-YAP/TAZ pathway is vital for AT2 to AT1 development and dysregulation of this pathway is a key feature of idiopathic pulmonary fibrosis. In a mouse model, AT2 cells lacking YAP/TAZ were injured with bleomycin. scRNA-Seq showed upregulated fibroblast activation markers, increased fibrillar collagen expression, and prolonged inflammation 28 days post-injury, ultimately resulting in lung fibrosis.

Spatial molecular imaging is combined with single-cell sequencing to characterize the tumor microenvironment of human pancreatic cancer. These multi-modal data lead to the generation of the SCOTIA model to better explain the emergence of treatment resistance.

Using an organoid and mouse model of SHH medulloblastoma (MB), scRNA-seq data shows tumor cells expressing the reoccurrence driver OLIG2, are disrupted by CT-179 with minimal off-target toxicity. Post-treatment, tumors up-regulate CDK4 mediating CT-179 resistance. However, combined therapy with a CDK4/6 inhibitor delayed cancer recurrence compared to either single agent.

Using scRNA-seq, researchers developed a scalable screening platform to establish a morphogen atlas of human neural cell fate. By applying 14 morphogen modulators to neural organoids, they identified distinct cellular and structural characteristics of brain regions and critical timing windows.

Using scRNA-seq data of CD4+ T cells from healthy individuals and autoimmune disease patients, clustering was performed through non-negative matrix factorization (NMF). Analysis of publicly available scRNA-seq datasets identified 12 transcriptional gene programs that characterized each autoimmune disease and predicted clinical status accurately.

To enhance research into BHV-1, authors developed a 3-D matrix system for bovine tracheal organoid culture. scRNA-seq data showed vulnerability to BHV-1 virus and robust immune response to stimulation by Pam2Cys, demonstrating the utility of the 3-D model system in studying viral infections.

Human Mesenchymal Stem Cells (hMSC) modulate T cells and macrophages when administered into a Chron’s disease model. scRNA-seq showed long-term anti-inflammatory macrophage reprogramming, providing evidence of prolonged therapeutic effects of hMSC.

In a hepatic organoid model, scRNA-seq identified the liver fibrosis-inducing ligand. TGFβ1 exposure transformed mesenchymal cells into myofibroblast-like cells, upregulating proteases, anti-proteases, and extracellular matrix genes, thereby promoting liver fibrosis development.

Introduces FAVA, a novel analysis method to handle large-scale scRNA-seq and proteomic data, predict high-confidence functional associations, and provide good coverage for understudied proteins. Performance was evaluated using freely available proteomic and PBMC scRNA-Seq datasets.

In COVID-19-infected human sensory neurons, scRNA-seq was critical in revealing that sensory neurons can be infected by SARS-CoV-2 but are unable to produce new viruses. This may have implications for understanding the infection’s long-term impact on the peripheral nervous system.

In a zebrafish model of progressive retinal degeneration, inflammation alone was not sufficient to trigger Müller glia reprogramming into multipotent retinal progenitors. Single cell RNA-seq showed that notch signaling remained active with progressive degeneration in contrast to what has been seen previously with acute injury.

A detailed performance evaluation of Evercode™ WT v2 that highlights improved gene and transcript detection, robustness across samples, and no bias in gene expression data. Multiple sample types were assessed, including cells and nuclei.

Transcriptomic studies on prion-infected mouse brains revealed gene signatures similar to human prion disease, shedding light on underlying molecular mechanisms. By introducing a protein denaturation step, samples could be transferred from a BSL-3 to a BSL-2 lab for library preparation and sequencing.

Two transcription factors required for developing ovarian granulosa cells - previously lacking components of human ovary organoids - were identified. Human iPSCs were induced to differentiate into human ovary organoids, whose identities were confirmed based on differential gene expression.

Microglia are brain cells with a role in Alzheimer’s Disease development and progression. A knock-out mouse model revealed a role for microglia in protecting brains by removing calcium deposits.

Full length transcript isoforms were identified using long-read sequencing on the PacBio platform with a protocol modification described as LR-Split-Seq. Applying this approach in mouse muscle cell lines, previously known and novel alternatively spliced transcript isoforms were detected.