A Pax3 lineage gives rise to transient haematopoietic progenitors.

During embryonic development, muscle tissues, skin, and a subset of vascular endothelial cells arise from Pax3-expressing embryonic progenitors defined as paraxial mesoderm. By contrast, haemogenic potential is well established for extra-embryonic mesoderm and intra-embryonic lateral plate mesoderm, which do not express Pax3. To date, it is not known whether the haematopoietic system also contains Pax3 lineage cells.

The BulkECexplorer compiles endothelial bulk transcriptomes to predict functional versus leaky transcription.

Transcriptomic data can be mined to understand the molecular activity of cell types. Yet, functional genes may remain undetected in RNA sequencing (RNA-seq) experiments for technical reasons, such as insufficient read depth or gene dropout. Conversely, RNA-seq experiments may detect lowly expressed mRNAs thought to be biologically irrelevant products of leaky transcription.

Electrocardiogram-gated Kilohertz Visualisation (EKV) Ultrasound Allows Assessment of Neonatal Cardiac Structural and Functional Maturation and Longitudinal Evaluation of Regeneration After Injury.

The small size and high heart rate of the neonatal mouse heart makes structural and functional characterisation particularly challenging. Here, we describe application of electrocardiogram-gated kilohertz visualisation (EKV) ultrasound imaging with high spatio-temporal resolution to non-invasively characterise the post-natal mouse heart during normal growth and regeneration after injury. The 2-D images of the left ventricle (LV) acquired across the cardiac cycle from post-natal day 1 (P1) to P42 revealed significant changes in LV mass from P8 that coincided with a switch from hyperplastic to hypertrophic growth and correlated with ex vivo LV weight.

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges.

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish.

Mechanisms and Therapeutic Targets of Cardiac Regeneration: Closing the Age Gap.

While a regenerative response is limited in the mammalian adult heart, it has been recently shown that the neonatal mammalian heart possesses a marked but transient capacity for regeneration after cardiac injury, including myocardial infarction. These findings evidence that the mammalian heart still retains a regenerative capacity and highlights the concept that the expression of distinct molecular switches (that activate or inhibit cellular mechanisms regulating tissue development and regeneration) vary during different stages of life, indicating that cardiac regeneration is an age-dependent process. Thus, understanding the mechanisms underpinning regeneration in the neonatal-infarcted heart is crucial to develop new treatments aimed at improving cardiovascular regeneration in the adult.

Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling.

The role of smooth muscle endothelin (ET) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ET receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ET receptors were selectively deleted from smooth muscle by crossing floxed ET mice with those expressing cre-recombinase controlled by the transgelin promoter.

Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium.

Corticosteroids influence the development and function of the heart and its response to injury and pressure overload via actions on glucocorticoid (GR) and mineralocorticoid (MR) receptors. Systemic corticosteroid concentration depends largely on the activity of the hypothalamic-pituitary-adrenal (HPA) axis, but glucocorticoid can also be regenerated from intrinsically inert metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), selectively increasing glucocorticoid levels within cells and tissues. Extensive studies have revealed the roles for glucocorticoid regeneration by 11β-HSD1 in liver, adipose, brain and other tissues, but until recently, there has been little focus on the heart.

The adult murine heart has a sparse, phagocytically active macrophage population that expands through monocyte recruitment and adopts an 'M2' phenotype in response to Th2 immunologic challenge.

Tissue resident macrophages have vital homeostatic roles in many tissues but their roles are less well defined in the heart. The present study aimed to identify the density, polarisation status and distribution of macrophages in the healthy murine heart and to investigate their ability to respond to immune challenge. Histological analysis of hearts from CSF-1 receptor (csf1-GFP; MacGreen) and CX3CR1 (Cx3cr1(GFP/+)) reporter mice revealed a sparse population of GFP positive macrophages that were evenly distributed throughout the left and right ventricular free walls and septum.