Analysis of cellular NO-GC expression in the murine heart and lineage determination in angiotensin II-induced fibrosis.

NO-sensitive guanylyl cyclase (NO-GC) is involved in the (patho)physiology of the mammalian heart. However, little is known about the individual cardiac cell types that express NO-GC and the role of the enzyme in cardiac fibrosis. Here, we describe the cellular expression of NO-GC in healthy and fibrotic murine myocardium; these data were compared with scRNA-seq data.

SARS-CoV-2-induced cytokine storm drives prolonged testicular injury and functional impairment in mice that are mitigated by dexamethasone.

Compromised male reproductive health, including reduced testosterone and sperm count, is one of the long COVID symptoms in individuals recovering from mild-severe disease. COVID-19 patients display testicular injury in the acute stage and altered serum fertility markers in the recovery phase, however, long-term implications on the testis remain unknown. This study characterized the consequences of SARS-CoV-2 on testis function.

RGD peptide promotes follicle growth through integrins αvβ3/αvβ5 in three-dimensional culture.

In Brief: Three-dimensional ovarian tissue culture is a unique model to define the effects of molecules on folliculogenesis. Using this model, we determined that RGD-integrin interaction plays a role in antrum formation and theca cell differentiation.

Abstract: We recently developed a three-dimensional (3D) ovarian tissue culture system supported by bacterial-derived dextran hydrogel.

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

Background: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear.

Methods: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration.

Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV.

While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV-) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry.

Fibroblast-specific inflammasome activation predisposes to atrial fibrillation.

Background: Recent work has shown that the NLR-family-pyrin-domain-containing 3 (NLRP3) inflammasome is expressed in cardiomyocytes and when specifically activated causes atrial electrical remodeling and arrhythmogenicity. Whether the NLRP3-inflammasome system is functionally important in cardiac fibroblasts (FBs) remains controversial. In this study, we sought to uncover the potential contribution of FB NLRP3-inflammasome signaling to the control of cardiac function and arrhythmogenesis.

In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury.

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ injury including testicular inflammation, reduced testosterone, and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells, however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury could be initiated by direct virus infection or exposure to systemic inflammatory mediators or viral antigens.

Corrigendum: Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequelae of SARS-CoV-2 infection.

[This corrects the article DOI: 10.3389/fimmu.2022.

Fibroblast and Immune Cell Cross-Talk in Cardiac Fibrosis.

Purpose Of Review: The intricate interplay between inflammatory and reparative responses in the context of heart injury is central to the pathogenesis of heart failure. Recent clinical studies have shown the therapeutic benefits of anti-inflammatory strategies in the treatment of cardiovascular diseases. This review provides a comprehensive overview of the cross-talk between immune cells and fibroblasts in the diseased heart.

Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection.

Background: Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored.

Methods: Using participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry.

In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury.

The hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ failure including testicular injury and germ cell depletion. The ACE2 receptor is also expressed in the resident testicular cells however, SARS-CoV-2 infection and mechanisms of testicular injury are not fully understood. The testicular injury can likely result either from direct virus infection of resident cells or by exposure to systemic inflammatory mediators or virus antigens.

Consequences of PDGFRα fibroblast reduction in adult murine hearts.

Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury.

Fibroblast GSK-3α Promotes Fibrosis via RAF-MEK-ERK Pathway in the Injured Heart.

Background: Heart failure is the leading cause of mortality, morbidity, and health care expenditures worldwide. Numerous studies have implicated GSK-3 (glycogen synthase kinase-3) as a promising therapeutic target for cardiovascular diseases. GSK-3 isoforms seem to play overlapping, unique and even opposing functions in the heart.

Regulation of extracellular matrix composition by fibroblasts during perinatal cardiac maturation.

Background: Cardiac fibroblasts are the main non-myocyte population responsible for extracellular matrix (ECM) production. During perinatal development, fibroblast expansion coincides with the transition from hyperplastic to hypertrophic myocardial growth. Therefore, we investigated the consequences of fibroblast loss at the time of cardiomyocyte maturation by depleting fibroblasts in the perinatal mouse.

TCF21 mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice.

Testicular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21.

Blockade of Fibroblast YAP Attenuates Cardiac Fibrosis and Dysfunction Through MRTF-A Inhibition.

Fibrotic remodeling of the heart in response to injury contributes to heart failure, yet therapies to treat fibrosis remain elusive. Yes-associated protein (YAP) is activated in cardiac fibroblasts by myocardial infarction, and genetic inhibition of fibroblast YAP attenuates myocardial infarction-induced cardiac dysfunction and fibrosis. YAP promotes myofibroblast differentiation and associated extracellular matrix gene expression through engagement of TEA domain transcription factor 1 and subsequent de novo expression of myocardin-related transcription factor A.

Cardiac Fibroblast Diversity.

Cardiac fibrosis is a pathological condition that occurs after injury and during aging. Currently, there are limited means to effectively reduce or reverse fibrosis. Key to identifying methods for curbing excess deposition of extracellular matrix is a better understanding of the cardiac fibroblast, the cell responsible for collagen production.

Developmental Pathways of Cardiac Fibroblasts.

Cardiac fibroblasts and fibrosis contribute to the pathogenesis of heart failure, a prevalent cause of mortality. Therefore, a majority of the existing information regarding cardiac fibroblasts is focused on their function and behavior after heart injury. Less is understood about the signaling and transcriptional networks required for the development and homeostatic roles of these cells.

Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis.

In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed 'fibromyocytes', rather than into a classical macrophage phenotype.

Platelet-derived growth factor receptor-α is essential for cardiac fibroblast survival.

Platelet-derived growth factor receptor α (PDGFRα), a receptor tyrosine kinase required for cardiac fibroblast development, is uniquely expressed by fibroblasts in the adult heart. Despite the consensus that PDGFRα is expressed in adult cardiac fibroblasts, we know little about its function when these cells are at rest. Here, we demonstrate that loss of PDGFRα in cardiac fibroblasts resulted in a rapid reduction of resident fibroblasts.

A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq.

Spermatogenesis requires intricate interactions between the germline and somatic cells. Within a given cross section of a seminiferous tubule, multiple germ and somatic cell types co-occur. This cellular heterogeneity has made it difficult to profile distinct cell types at different stages of development.

Cardiac fibroblasts: from origin to injury.

The cardiac fibroblast has essential roles in production and maintenance of extracellular matrix. While its role in maladaptive myocardial remodeling has been a focus of many studies, the cardiac fibroblast has become a topic of great interest as a contributor to heart physiology and as a therapeutic target. Recent reports are changing how we view and study the cardiac fibroblast by providing greater insights into fibroblast biology using refined techniques for fibroblast identification and manipulation.