HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow-derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation.

Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues.

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation.

The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.

Background: Ménière's disease (MD) is a disorder of the inner ear that causes episodic bouts of severe dizziness, roaring tinnitus, and fluctuating hearing loss. To date, no targeted therapy exists. As such, we have undertaken a large whole genome sequencing study on carefully phenotyped unilateral MD patients with the goal of gene/pathway discovery and a move towards targeted intervention.

Defining the relationship of salivary gland malignancies to novel cell subpopulations in human salivary glands using single nucleus RNA-sequencing.

Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin.

High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia.

Introduction: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries.

Methods: To elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries.

Results: Previously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries.

Targeting Clic1 for the treatment of obesity: A novel therapeutic strategy to reduce food intake and body weight.

Objective: Despite great advances in obesity therapeutics in recent years, there is still a need to identify additional therapeutic targets for the treatment of this disease. We previously discovered a signature of genes, including Chloride intracellular channel 1 (Clic1), whose expression was associated with drug-induced weight gain, and in these studies, we assess the effect of Clic1 inhibition on food intake and body weight in mice.

Methods: We studied the impact of Clic1 inhibition in mouse models of binge-eating, diet-induced obese mice and genetic models of obesity (Magel2 KO mice).

Identification of adipose tissue transcriptomic memory of anorexia nervosa.

Background: Anorexia nervosa (AN) is a complex debilitating disease characterized by intense fear of weight gain and excessive exercise. It is the deadliest of any psychiatric disorder with a high rate of recidivism, yet its pathophysiology is unclear. The Activity-Based Anorexia (ABA) paradigm is a widely accepted mouse model of AN that recapitulates hypophagia and hyperactivity despite reduced body weight, however, not the chronicity.

Transcriptional time course after rotator cuff repair in 6 month old female rabbits.

Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair ( = 4/group).

Maladaptive lymphangiogenesis is associated with synovial iron accumulation and delayed clearance in factor VIII-deficient mice after induced hemarthrosis.

Background: Mechanisms of iron clearance from hemophilic joints are unknown.

Objectives: To better understand mechanisms of iron clearance following joint bleeding in a mouse model of hemophilia.

Methods: Hemarthrosis was induced by subpatellar puncture in factor VIII (FVIII)-deficient (FVII) mice, +/- periprocedural recombinant human FVIII, and hypocoagulable (BALB/c) mice.

Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools.

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.

Spatial transcriptomics tools allow for regional exploration of heterogeneous muscle pathology in the pre-clinical rabbit model of rotator cuff tear.

Background: Conditions affecting skeletal muscle, such as chronic rotator cuff tears, low back pain, dystrophies, and many others, often share changes in muscle phenotype: intramuscular adipose and fibrotic tissue increase while contractile tissue is lost. The underlying changes in cell populations and cell ratios observed with these phenotypic changes complicate the interpretation of tissue-level transcriptional data. Novel single-cell transcriptomics has limited capacity to address this problem because muscle fibers are too long to be engulfed in single-cell droplets and single nuclei transcriptomics are complicated by muscle fibers' multinucleation.

The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.

Immaturity of alveolar macrophages (AMs) around birth contributes to the susceptibility of newborns to lung disease. However, the molecular features differentiating neonatal and mature, adult AMs are poorly understood. In this study, we identify the unique transcriptomes and enhancer landscapes of neonatal and adult AMs in mice.

Corrigendum: Transcriptional Time Course After Rotator Cuff Tear.

[This corrects the article DOI: 10.3389/fphys.2021.

Wastewater and surface monitoring to detect COVID-19 in elementary school settings: The Safer at School Early Alert project.

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.

ANT2 drives proinflammatory macrophage activation in obesity.

Macrophage proinflammatory activation is an important etiologic component of the development of insulin resistance and metabolic dysfunction in obesity. However, the underlying mechanisms are not clearly understood. Here, we demonstrate that a mitochondrial inner membrane protein, adenine nucleotide translocase 2 (ANT2), mediates proinflammatory activation of adipose tissue macrophages (ATMs) in obesity.

Transcriptional Time Course After Rotator Cuff Tear.

Rotator cuff (RC) tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration in the chronic state, which is not improved with intervention or surgical repair. This highlights the need to better understand the underlying dysfunction in muscle after RC tendon tear.

Differential blood DNA methylation across Lewy body dementias.

Introduction: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.

Strategies to Identify Mesenchymal Stromal Cells in Minimally Manipulated Human Bone Marrow Aspirate Concentrate Lack Consensus.

Background: There is a need to identify and quantify mesenchymal stromal cells (MSCs) in human bone marrow aspirate concentrate (BMAC) source tissues, but current methods to do so were established in cultured cell populations. Given that surface marker and gene expression change in cultured cells, it is doubtful that these strategies are valid to quantify MSCs in fresh BMAC.

Purpose: To establish the presence, quantity, and heterogeneity of BMAC-derived MSCs in minimally manipulated BMAC using currently available strategies.

Inflammation-driven deaminase deregulation fuels human pre-leukemia stem cell evolution.

Inflammation-dependent base deaminases promote therapeutic resistance in many malignancies. However, their roles in human pre-leukemia stem cell (pre-LSC) evolution to acute myeloid leukemia stem cells (LSCs) had not been elucidated. Comparative whole-genome and whole-transcriptome sequencing analyses of FACS-purified pre-LSCs from myeloproliferative neoplasm (MPN) patients reveal APOBEC3C upregulation, an increased C-to-T mutational burden, and hematopoietic stem and progenitor cell (HSPC) proliferation during progression, which can be recapitulated by lentiviral APOBEC3C overexpression.

Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h.

Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling components, genes essential for HSPC development, due to abrogated transcription.

Deletion of the Gene Encoding the NMDA Receptor GluN1 Subunit in Schwann Cells Causes Ultrastructural Changes in Remak Bundles and Hypersensitivity in Pain Processing.

Abnormalities in interactions between sensory neurons and Schwann cells (SCs) may result in heightened pain processing and chronic pain states. We previously reported that SCs express the NMDA receptor (NMDA-R), which activates cell signaling in response to glutamate and specific protein ligands, such as tissue-type plasminogen activator. Herein, we genetically targeted encoding the essential GluN1 NMDA-R subunit, conditionally in SCs, to create a novel mouse model in which SCs are NMDA-R-deficient (GluN1- mice).

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection.

Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified.

Differential expression of nuclear genes encoding mitochondrial proteins from urban and rural populations in Morocco.

Urbanization in low-income countries represents an important inflection point in the epidemiology of disease, with rural populations experiencing high rates of chronic and recurrent infections and urban populations displaying a profile of noncommunicable diseases. To investigate if urbanization alters the expression of genes encoding mitochondrial proteins, we queried gene microarray data from rural and urban populations living in Morocco (GSE17065). The R Bioconductor packages edgeR and limma were used to identify genes with different expression.

Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury.

The goal of stem cell therapy for spinal cord injury (SCI) is to restore motor function without exacerbating pain. Induced pluripotent stem cells (iPSC) may be administered by autologous transplantation, avoiding immunologic challenges. Identifying strategies to optimize iPSC-derived neural progenitor cells (hiNPC) for cell transplantation is an important objective.