Causal machine learning for single-cell genomics.

Advances in single-cell '-omics' allow unprecedented insights into the transcriptional profiles of individual cells and, when combined with large-scale perturbation screens, enable measuring of the effect of targeted perturbations on the whole transcriptome. These advances provide an opportunity to better understand the causative role of genes in complex biological processes. In this Perspective, we delineate the application of causal machine learning to single-cell genomics and its associated challenges.

Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex.

Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature.

Smoking increases expression of the SARS-CoV-2 spike protein-binding long ACE2 isoform in bronchial epithelium.

After more than two years the COVID-19 pandemic, that is caused by infection with the respiratory SARS-CoV-2 virus, is still ongoing. The risk to develop severe COVID-19 upon SARS-CoV-2 infection is increased in individuals with a high age, high body mass index, and who are smoking. The SARS-CoV-2 virus infects cells of the upper respiratory tract by entering these cells upon binding to the Angiotensin-converting enzyme 2 (ACE2) receptor.

TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.

Decreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43) condensates. Granulin-mediated clearance of both lipid droplets and TDP-43 condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration.

Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa.

Background: Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies.

Methods: Primary bronchial epithelial cells (PBEC) were differentiated at the air-liquid interface (ALI) and exposed to whole CS.

Origin and function of activated fibroblast states during zebrafish heart regeneration.

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis.

Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development.

Maldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development.

Sfaira accelerates data and model reuse in single cell genomics.

Single-cell RNA-seq datasets are often first analyzed independently without harnessing model fits from previous studies, and are then contextualized with public data sets, requiring time-consuming data wrangling. We address these issues with sfaira, a single-cell data zoo for public data sets paired with a model zoo for executable pre-trained models. The data zoo is designed to facilitate contribution of data sets using ontologies for metadata.

AutoGeneS: Automatic gene selection using multi-objective optimization for RNA-seq deconvolution.

Knowing cell-type proportions in a tissue is very important to identify which cells or cell types are targeted by a disease or perturbation. Hence, several deconvolution methods have been proposed to infer cell-type proportions from bulk RNA samples. Their performance with noisy reference profiles and closely correlated cell types highly depends on the set of genes undergoing deconvolution.

Comparison of genome-wide gene expression profiling by RNA Sequencing microarray in bronchial biopsies of COPD patients before and after inhaled corticosteroid treatment: does it provide new insights?

https://bit.ly/2N8sY3s.

Current Smoking Alters Gene Expression and DNA Methylation in the Nasal Epithelium of Patients with Asthma.

Current smoking contributes to worsened asthma prognosis and more severe symptoms and limits the beneficial effects of corticosteroids. As the nasal epithelium can reflect smoking-induced changes in the lower airways, it is a relevant source to investigate changes in gene expression and DNA methylation. This study explores gene expression and DNA methylation changes in current and ex-smokers with asthma.

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology.