scholarly journals The earliest metanephric arteriolar progenitors and their role in kidney vascular development

2015 ◽  
Vol 308 (2) ◽  
pp. R138-R149 ◽  
Author(s):  
Maria Luisa S. Sequeira-Lopez ◽  
Eugene E. Lin ◽  
Minghong Li ◽  
Yan Hu ◽  
Curt D. Sigmund ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Types ◽  
Forkhead Transcription Factor ◽  
Arterial Tree ◽  
Mural Cells ◽  
Vascular Morphogenesis ◽  
Distinct Cell ◽  
Series Of Experiments ◽  
Renal Vascular

The development of the kidney arterioles is poorly understood. Mature arterioles contain several functionally and morphologically distinct cell types, including smooth muscle, endothelial, and juxtaglomerular cells, and they are surrounded by interconnected pericytes, fibroblasts, and other interstitial cells. We have shown that the embryonic kidney possesses all of the necessary precursors for the development of the renal arterial tree, and those precursors assemble in situ to form the kidney arterioles. However, the identity of those precursors was unclear. Within the embryonic kidney, several putative progenitors marked by the expression of either the winged-forkhead transcription factor 1 (Foxd1+ progenitor), the aspartyl-protease renin (Ren+ progenitor), and/or hemangioblasts (Scl+ progenitor) are likely to differentiate and endow most of the cells of the renal arterial tree. However, the lineage relationships and the role of these distinct progenitors in renal vascular morphogenesis have not been delineated. We, therefore, designed a series of experiments to ascertain the hierarchical lineage relationships between Foxd1+ and Ren+ progenitors and the role of these two precursors in the morphogenesis and patterning of the renal arterial tree. Results show that 1) Foxd1+ cells are the precursors for all the mural cells (renin cells, smooth muscle cells, perivascular fibroblasts, and pericytes) of the renal arterial tree and glomerular mesangium, and 2) Foxd1 per se directs the origin, number, orientation, and cellular composition of the renal vessels.

Abstract 23: Foxd1+ Stromal Cells, the Required Progenitors for Kidney Vascular Development

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Eugene E Lin ◽  
Roberto A Gomez ◽  
Maria-Luisa S Sequeira-Lopez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Cell Types ◽  
Lineage Tracing ◽  
Arterial Tree ◽  
Mural Cell ◽  
Mural Cells ◽  
Selective Ablation ◽  
Similar Phenotype

The mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have previously suggested using detailed lineage tracing that renal stromal cells, characterized by their early and transient expression of the transcription factor Foxd1 , give rise to the entirety of the mural cell layer of the renal arterial tree and mesangial cells. Mural cells as defined here exclude endothelial cells, which we identified as having a separate precursor, the renal hemangioblast. To define whether Foxd1 cells are the required essential progenitor or whether their role as such could be assumed by other cell types, we used the cre-lox system to generate mice expressing diphtheria toxin subunit A in Foxd1+ cells ( Foxd1-DTA mice ) which resulted in animals with selective ablation of Foxd1+ cells. Kidneys from Foxd1-DTA embryos had a significantly reduced complement of arterial mural cells, lacking smooth muscle cells, perivascular fibroblasts, renin cells and mesangial cells. Interestingly, the few vessels that remained were also abnormal: they originated underneath the kidney capsule and elongated towards the center of the kidney rather than radiating outward from the center of the kidney. In addition, ablation of Foxd1 cells resulted in significantly delayed nephrogenesis and reduction in glomerular number. In conjunction with our previous data showing a similar phenotype upon global deletion of the Foxd1 ,gene, this illustrates the central role of Foxd1 and the cells that express it during early development. We conclude that Foxd1 stromal cells are the required progenitors for the establishment of the mural cells of the kidney arterioles and (via Foxd1 expression) for the proper origin and orientation of the kidney vessels.

Abstract 238: ABCA1 and HDL3 are Required to Modulate Smooth Muscle Cells Trandifferentiation in a Myocardin-miR143/145-dependent Process

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Silvia Castiglioni ◽  
Alessio Vettore ◽  
Lorenzo Arnaboldi ◽  
Laura Calabresi ◽  
Alberto Corsini ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Foam Cells ◽  
Knock Out ◽  
Phenotypic Changes ◽  
Basal Expression ◽  
Basal Expression Level

Cells of the artery wall may accumulate free cholesterol and cholesteryl esters becoming foam cells. Up to 50% of foam cells in human lesions originates from smooth muscle cells (SMCs). Arterial SMCs express the ATP binding cassette (ABC) transporter ABCA1 and, upon cholesterol loading, express macrophage markers and a phagocytic activity. To characterize the role of ABCA1 and HDL3 in this transdifferentiation process, we evaluated the phenotypic changes in SMCs isolated from wild type (WT) and ABCA1 knock out (KO) mice and how HDL3 affects these changes. Cholesterol loading causes the downregulation of the expression of SMC markers including ACTA2, alpha-tropomyosin and myosin heavy chain and increases the expression of macrophage-related genes such as CD68, Mac-2, SRB1, MMPs, ABCG1 and ABCA1. HDL3 treatment in WT cells is able to normalize the expression of ACTA2, while the expression of macrophage-related genes is reduced. On the contrary, the preventive effect of HDL3 is completely lost in ABCA1 KO cells. Interestingly, the presence of HDL3 does not differently affect neutral lipid accumulation in WT or ABCA1 KO cells but stimulates phospholipids removal only in WT cells. ApoAI addition does not reverse the phenotypic changes induced by cholesterol not only in KO but also in WT cells. Moreover, cholesterol loading reduces the expression of myocardin, the master SMC specific-transcriptional coactivator involved in SMC differentiation, by up to 55% (p<0.01 vs respective control) in both cell types. HDL3 normalizes myocardin levels in WT cells while it does not have any effect in ABCA1 KO cells. Similar results are obtained evaluating the levels of miR-143/145, which positively regulate myocardin. The basal expression level of KLF4, a myocardin repressor, is almost double in ABCA1 KO cells compared to WT. After cholesterol loading, KLF4 is slightly reduced in WT cells, while its expression is halved in ABCA1 KO cells. HDL3 restores KLF4 to basal levels in KO cells, but it further reduces them in WT cells. These results indicate that HDL3, modulating the miR143/145-myocardin axis in SMC, prevents the cholesterol-induced gene expression modification regardless of its cholesterol unloading capacity and the presence of ABCA1 is required.

Abstract 256: Rbp-j Controls the Fate of the Kidney Vasculature

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Eugene Lin ◽  
Maria Luisa S Sequeira Lopez ◽  
Roberto A Gomez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Notch Signaling Pathway ◽  
Renal Vasculature ◽  
Arterial Tree ◽  
Mural Cells ◽  
Vascular Markers ◽  
Renal Abnormalities ◽  
Glomerular Tuft

Proper assembly of the renal vasculature is essential for post-natal life, and alterations to the renal vasculature are at the root of many types of cardiovascular disease. However, the mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have identified a population of renal stromal cells (marked by their expression of the transcription factor Foxd1) that differentiate to form the mural cells of the kidney arterial tree (excluding endothelial cells) and the glomerular mesangium. We previously demonstrated that RBP-J, the final transcriptional effector of the Notch signaling pathway, controls the phenotype of renin cells which are also derived from the Foxd1 lineage. We therefore hypothesized that RBP-J regulates the differentiation of stromal cells into the mural cells of the kidney arterioles. To answer this question, we deleted RBP-J in the metanephric stromal precursor cells, and found that mutant mice displayed striking kidney abnormalities in early life. Staining for vascular markers showed a significant decrease in the number of arteries and arterioles. Vessel walls were thinner due to a decrease in both the size and number of smooth muscle cells. We also noted a near absence of renin cells, supporting our earlier findings regarding the key role of RBP-J in establishing the differentiated renin cell endowment. These findings were accompanied by delayed nephrogenesis and other renal abnormalities including tubular dilation. In addition, mutant kidneys lacked Foxd1-lineage cells within the glomeruli, resulting in a depletion of mesangial cells and glomerular aneurysms. Thus, we conclude that RBP-J in Foxd1+ stromal cells plays a key role in the development of the kidney vasculature, and regulates the fate of cells that compose the arterial tree and the glomerular tuft.

scholarly journals Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages

2019 ◽  
Vol 116 (28) ◽  
pp. 14254-14259 ◽  
Author(s):  
Zhihong Chen ◽  
James L. Ross ◽  
Dolores Hambardzumyan
Keyword(s):  
Cell Types ◽  
Lineage Tracing ◽  
Response To Therapy ◽  
Vascular Endothelial ◽  
Distinct Cell ◽  
Attractive Option ◽  
Endothelial Growth Factor ◽  
Distinct Morphology ◽  
Cx3cr1 Expression

Characterized by a dismal survival rate and limited response to therapy, glioblastoma (GBM) remains one of the most aggressive human malignancies. Recent studies of the role of tumor-associated macrophages (TAMs) in the progression of GBMs have demonstrated that TAMs are significant contributors to tumor growth, invasion, and therapeutic resistance. TAMs, which include brain-resident microglia and circulating bone marrow derived-monocytes (BMDMs), are typically grouped together in histopathological and molecular analyses due to the lack of reliable markers of distinction. To develop more effective therapies aimed at specific TAM populations, we must first understand how these cells differ both morphologically and behaviorally. Furthermore, we must develop a deeper understanding of the mechanisms encouraging their infiltration and how these mechanisms can be therapeutically exploited. In this study, we combined immunocompetent lineage tracing mouse models of GBM with high-resolution open-skull 2-photon microscopy to investigate the phenotypical and functional characteristics of TAMs. We demonstrate that TAMs are composed of 2 morphologically distinct cell types that have differential migratory propensities. We show that BMDMs are smaller, minimally branched cells that are highly migratory compared with microglia, which are larger, highly branched stationary cells. In addition, 2 populations of monocytic macrophages were observed that differed in terms of CX3CR1 expression and migratory capacity. Finally, we demonstrate the efficacy of anti-vascular endothelial growth factor A blockade for prohibiting TAM infiltration, especially against BMDMs. Taken together, our data clearly define characteristics of individual TAM populations and suggest that combination therapy with antivascular and antichemotaxis therapy may be an attractive option for treating these tumors.

scholarly journals Organizational Hierarchy and Structural Diversity of Microvascular Pericytes in Adult Mouse Cortex

2017 ◽  
Author(s):  
Roger I. Grant ◽  
David A. Hartmann ◽  
Robert G. Underly ◽  
Andrée-Anne Berthiaume ◽  
Narayan R. Bhat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Cell Types ◽  
Mural Cell ◽  
Mural Cells ◽  
Mouse Cortex ◽  
Transitional Cells ◽  
Brain Microvasculature

ABSTRACTSmooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 156-170 ◽  
Author(s):  
Ye Chun Ruan ◽  
Wenliang Zhou ◽  
Hsiao Chang Chan
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Contraction ◽  
Cell Types ◽  
Smooth Muscle Contraction ◽  
Organ Systems ◽  
Wide Range ◽  
Important Regulator

As an analog to the endothelium situated next to the vascular smooth muscle, the epithelium is emerging as an important regulator of smooth muscle contraction in many vital organs/tissues by interacting with other cell types and releasing epithelium-derived factors, among which prostaglandins have been demonstrated to play a versatile role in governing smooth muscle contraction essential to the physiological and pathophysiological processes in a wide range of organ systems.

scholarly journals Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 593
Author(s):  
Alexander Lin ◽  
Niridu Jude Peiris ◽  
Harkirat Dhaliwal ◽  
Maria Hakim ◽  
Weizhen Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neurodegenerative Diseases ◽  
Structural Integrity ◽  
Vascular System ◽  
Vascular Wall ◽  
Cell Plasticity ◽  
Mural Cell ◽  
Mural Cells ◽  
Heterogenous Population

Mural cells collectively refer to the smooth muscle cells and pericytes of the vasculature. This heterogenous population of cells play a crucial role in the regulation of blood pressure, distribution, and the structural integrity of the vascular wall. As such, dysfunction of mural cells can lead to the pathogenesis and progression of a number of diseases pertaining to the vascular system. Cardiovascular diseases, particularly atherosclerosis, are perhaps the most well-described mural cell-centric case. For instance, atherosclerotic plaques are most often described as being composed of a proliferative smooth muscle cap accompanied by a necrotic core. More recently, the role of dysfunctional mural cells in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, is being recognized. In this review, we begin with an exploration of the mechanisms underlying atherosclerosis and neurodegenerative diseases, such as mural cell plasticity. Next, we highlight a selection of signaling pathways (PDGF, Notch and inflammatory signaling) that are conserved across both diseases. We propose that conserved mural cell signaling mechanisms can be exploited for the identification or development of dual-pronged therapeutics that impart both cardio- and neuroprotective qualities.

scholarly journals The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

2021 ◽  
Vol 10 (15) ◽  
pp. 3348
Author(s):  
Angela Quispe-Salcedo ◽  
Hayato Ohshima
Keyword(s):  
Dendritic Cells ◽  
Cell Types ◽  
Tooth Injuries ◽  
Tertiary Dentin ◽  
Distinct Cell ◽  
Reparative Dentin ◽  
Pulp Cells ◽  
Antigen Presenting

The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of “dentin-pulp immunology” is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.

Sign in / Sign up

Export Citation Format

Share Document