scholarly journals Contribution of a GATA4-Expressing Hematopoietic Progenitor Lineage to the Adult Mouse Endothelium

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1257
Author(s):  
Rita Carmona ◽  
Sandra Díaz del Moral ◽  
Silvia Barrena ◽  
Ramón Muñoz-Chápuli
Keyword(s):  
Adult Mouse ◽  
Fetal Liver ◽  
Coronary Vessels ◽  
Blood Stream ◽  
Circulating Cells ◽  
Embryonic Origin ◽  
Coronary Endothelial Cells ◽  
Coronary Endothelium ◽  
Different Sources ◽  
Mesodermal Lineage

Different sources have been claimed for the embryonic origin of the coronary endothelium. Recently, the potential of circulating cells as progenitors of the cardiac endothelium has also been suggested. In a previous study we have shown that circulating progenitors are recruited by the embryonic endocardium and incorporated into the coronary vessels. These progenitors derive from a mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2. Herein, we aim to trace this specific lineage throughout postnatal stages. We have found that more than 50% of the adult cardiac endothelium derives from the G2-GATA4 lineage. This percentage increases from embryos to adults probably due to differential proliferation and postnatal recruitment of circulating endothelial progenitors. In fact, injection of fetal liver or placental cells in the blood stream of neonates leads to incorporation of G2-GATA4 lineage cells to the coronary endothelium. On the other hand, labeling of the hematopoietic lineage by the stage E7.5 also resulted in positive coronary endothelial cells from both, embryos and adults. Our results suggest that early hematopoietic progenitors recruited by the embryonic ventricular endocardium can become the predominant source of definitive endothelium during the vascularization of the heart.

scholarly journals Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

1995 ◽  
Vol 15 (2) ◽  
pp. 671-681 ◽  
Author(s):  
A E Sollbach ◽  
G E Wu
Keyword(s):  
Heavy Chain ◽  
Adult Mouse ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Antigen Receptors ◽  
Adult Mice ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Fetal Liver Cells

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

scholarly journals Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development

2021 ◽  
Author(s):  
Ragini S Phansalkar ◽  
Josephine Krieger ◽  
Mingming Zhao ◽  
Sai Saroja Kolluru ◽  
Robert C Jones ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cell Fate ◽  
Adult Mouse ◽  
Coronary Vessels ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Cell Type ◽  
Functional Differences ◽  
Coronary Blood Vessels ◽  
Two Populations

Most cell fate trajectories during development follow a diverging, tree-like branching pattern, but the opposite can occur when distinct progenitors contribute to the same cell type. During this convergent differentiation, it is unknown if cells "remember" their origins transcriptionally or whether this influences cell behavior. Most coronary blood vessels of the heart develop from two different progenitor sources-the endocardium (Endo) and sinus venosus (SV)-but whether transcriptional or functional differences related to origin are retained is unknown. We addressed this by combining lineage tracing with single-cell RNA sequencing (scRNAseq) in embryonic and adult mouse hearts. Shortly after coronary development begins, capillary ECs transcriptionally segregated into two states that retained progenitor-specific gene expression. Later in development, when the coronary vasculature is well-established but still remodeling, capillary ECs again segregated into two populations, but transcriptional differences were related to tissue localization rather than lineage. Specifically, ECs in the heart septum expressed genes indicative of increased local hypoxia and decreased blood flow. Adult capillary ECs were more homogeneous and lacked indications of either lineage or location. In agreement, SV- and Endo-derived ECs in adult hearts displayed similar responses to injury. Finally, scRNAseq of developing human coronary vessels indicated that the human heart followed similar principles. Thus, over the course of development, transcriptional heterogeneity in coronary ECs is first influenced by lineage, then by location, until heterogeneity disappears in the homeostatic adult heart. These results highlight the plasticity of ECs during development, and the validity of the mouse as a model for human coronary development.

NO produced by endothelial NO synthase is a mediator of delayed preconditioning-induced endothelial protection

2003 ◽  
Vol 284 (6) ◽  
pp. H2053-H2060 ◽  
Author(s):  
Karine Laude ◽  
Julie Favre ◽  
Christian Thuillez ◽  
Vincent Richard
Keyword(s):  
Ischemia Reperfusion ◽  
No Synthase ◽  
Cardiac Ischemia ◽  
Sham Surgery ◽  
Nos Inhibitor ◽  
Coronary Endothelial Cells ◽  
Cardiac Preconditioning ◽  
Coronary Endothelium ◽  
Inos Inhibition

Preconditioning with brief periods of ischemia-reperfusion (I/R) induces a delayed protection of coronary endothelial cells against reperfusion injury. We assessed the possible role of nitric oxide (NO) produced during prolonged I/R as a mediator of this endothelial protection. Anesthetized rats were subjected to 20-min cardiac ischemia/60-min reperfusion, 24 h after sham surgery or cardiac preconditioning (1 × 2-min ischemia/5-min reperfusion and 2 × 5-min ischemia/5-min reperfusion). The nonselective NO synthase (NOS) inhibitor l-NAME, the selective inhibitors of neuronal (7-nitroindazole) or inducible (1400W) NOS, or the peroxynitrite scavenger seleno-l-methionine were administered 10 min before prolonged ischemia. Preconditioning prevented the reperfusion-induced impairment of coronary endothelium-dependent relaxations to acetylcholine (maximal relaxation: sham 77 ± 3; I/R 44 ± 6; PC 74 ± 5%). This protective effect was abolished by l-NAME (41 ± 7%), whereas 7-NI, 1400W or seleno-l-methionine had no effect. The abolition of preconditioning by l-NAME, but not by selective nNOS or iNOS inhibition, suggests that NO produced by eNOS is a mediator of delayed endothelial preconditioning.

Evidence supporting the Nucleotide Axis Hypothesis: ATP release and metabolism by coronary endothelium

2001 ◽  
Vol 281 (4) ◽  
pp. H1657-H1666 ◽  
Author(s):  
Iain L. O. Buxton ◽  
Robert A. Kaiser ◽  
Brian C. Oxhorn ◽  
Dennis J. Cheek
Keyword(s):  
Endothelial Cells ◽  
Atp Release ◽  
Coronary Vessels ◽  
Nucleoside Diphosphate Kinase ◽  
Predicted Amino Acid Sequence ◽  
Western Blots ◽  
Cardiac Blood ◽  
Vasoactive Mediators ◽  
Regulation Of Activity ◽  
Coronary Endothelium

The Nucleotide Axis Hypothesis, defined and supported herein, proposes that ATP stimulates the release of vasoactive mediators from endothelium, including ATP itself. Here, we show rapid endothelium-dependent, agonist-stimulated ATP elaboration in coronary vessels of guinea pigs. Measurement of extracellular ADP metabolism in intact vessels results in the time- and substrate-dependent formation of ATP in the coronary perfusate in amounts greater than can be accounted for by release from endothelium alone. ATP formation by endothelial cells is saturable ( K M = 38.5 μmol/l, where K M is substrate concentration at which rate is half-maximal.) and trypsin-sensitive, membranes from [γ-32P]ATP-labeled cells support ADP-dependent transphosphorylation by a 20-kDa protein, Western blots reveal the presence of a nucleoside diphosphate kinase (NDPK) of ∼20 kDa in endothelial membranes, and analysis of NDPK antibody binding by flow cytometry is consistent with the presence of an ecto-NDPK on cardiac endothelial cells. Sequencing of the endothelial cell ecto-NDPK reveals a predicted amino acid sequence with 85% identity to human Nm23-H1 and consistent with a protein whose properties may confer membrane association as well as sites of regulation of activity. Our data underscore the potential importance of a nucleotide axis in cardiac blood vessels.

Endostatin uncouples NO and Ca2+response to bradykinin through enhanced O2−· production in the intact coronary endothelium

2005 ◽  
Vol 288 (2) ◽  
pp. H686-H694 ◽  
Author(s):  
Andrew Y. Zhang ◽  
Eric G. Teggatz ◽  
Ai-Ping Zou ◽  
William B. Campbell ◽  
Pin-Lan Li
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Speed ◽  
Imaging Techniques ◽  
No Synthase ◽  
No Production ◽  
Intracellular Ca ◽  
Coronary Endothelial Cells ◽  
Coronary Endothelium ◽  
O2 Production

The present study tested the hypothesis that endostatin stimulates superoxide (O2−·) production through a ceramide-mediating signaling pathway and thereby results in an uncoupling of bradykinin (BK)-induced increases in intracellular Ca2+concentration ([Ca2+]i) from nitric oxide (NO) production in coronary endothelial cells. With the use of high-speed, wavelength-switching, fluorescence-imaging techniques, the [Ca2+]iand NO levels were simultaneously monitored in the intact endothelium of freshly isolated bovine coronary arteries. Under control conditions, BK was found to increase NO production and [Ca2+]iin parallel. When the arteries were pretreated with 100 nM human recombinant endostatin for 1 h, this BK-induced NO production was reduced by 89%, whereas [Ca2+]iwas unchanged. With the conversion rate of l-[3H]arginine to l-[3H]citrulline measured, endostatin had no effect on endothelial NO synthase (NOS) activity, but it stimulated ceramide by activation of sphingomyelinase (SMase), whereby O2−· production was enhanced in endothelial cells. O2−· scavenging by tiron and inhibition of NAD(P)H oxidase by apocynin markedly reversed the effect of endostatin on the NO response to BK. These results indicate that endostatin increases intracellular ceramide levels, which enhances O2−· production through activation of NAD(P)H oxidase. This ceramide-O2−· signaling pathway may contribute importantly to endostatin-induced endothelial dysfunction.

scholarly journals Identification of Carbon Monoxide Levels

2020 ◽  
Vol 9 (4) ◽  
pp. 883-890
Keyword(s):  
Carbon Monoxide ◽  
Prediction Accuracy ◽  
Blood Stream ◽  
Simple System ◽  
Data Set ◽  
And Control ◽  
Different Sources ◽  
Harmful Effects ◽  
Pollutant Gases ◽  
Monitor And Control

With ever rising emission of pollutant gases from different sources like factories, auto mobiles and power, it is a subject of emerging concerns that some strong measures are required to monitor and control these pollutant. Breathing of these gases may cause serious harmful effects to anyone. In these gases, Carbon Monoxide (CO) is often called "Silent Killer" as being colour-less, odour-less and poisonous, it is undetectable by humans. When inhaled it, it deprives blood stream of oxygen and suffocates its victim. In this paper we are proposing a simple system to monitor Carbon Monoxide (CO). Carbon Monoxide (CO) detectors are used to detect CO. This paper also discusses analysis of amount of these CO based a data set from Kaggle and prediction of possible amount of CO in air using regression. The prediction accuracy which is measured as RMSE is 0.17766.

scholarly journals Prdm16 is a critical regulator of adult long-term hematopoietic stem cell quiescence

2020 ◽  
Vol 117 (50) ◽  
pp. 31945-31953
Author(s):  
Kristbjorn O. Gudmundsson ◽  
Nhu Nguyen ◽  
Kevin Oakley ◽  
Yufen Han ◽  
Bjorg Gudmundsdottir ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Fetal Liver ◽  
Annexin V ◽  
Conditional Knockout ◽  
Sequencing Analysis ◽  
Cell Cycle Regulators ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Knockout Mouse Model

Regulation of quiescence is critical for the maintenance of adult hematopoietic stem cells (HSCs). Disruption of transcription factor gene Prdm16 during mouse embryonic development has been shown to cause a severe loss of fetal liver HSCs; however, the underlying mechanisms and the function of Prdm16 in adult HSCs remain unclear. To investigate the role of Prdm16 in adult HSCs, we generated a novel conditional knockout mouse model and deleted Prdm16 in adult mouse hematopoietic system using the IFN-inducible Mx1-Cre. Our results show that Prdm16 deletion in the adult mouse hematopoietic system has a less severe effect on HSCs, causing a gradual decline of adult HSC numbers and a concomitant increase in the multipotent progenitor (MPP) compartment. Prdm16 deletion in the hematopoietic system following transplantation produced the same phenotype, indicating that the defect is intrinsic to adult HSCs. This HSC loss was also exacerbated by stress induced by 5-fluorouracil injections. Annexin V staining showed no difference in apoptosis between wild-type and knockout adult HSCs. In contrast, Bromodeoxyuridine analysis revealed that loss of Prdm16 significantly increased cycling of long-term HSCs (LT-HSCs) with the majority of the cells found in the S to G2/M phase. Consistently, RNA sequencing analysis of mouse LT-HSCs with and without Prdm16 deletion showed that Prdm16 loss induced a significant decrease in the expression of several known cell cycle regulators of HSCs, among which Cdkn1a and Egr1 were identified as direct targets of Prdm16. Our results suggest that Prdm16 preserves the function of adult LT-HSCs by promoting their quiescence.

Microgliosis in the Injured Brain

2015 ◽  
Vol 22 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Ting Li ◽  
Shengxiang Zhang
Keyword(s):  
Sole Source ◽  
Experimental Models ◽  
Supporting Evidence ◽  
Multiple Sources ◽  
Reactive Microglia ◽  
Circulating Cells ◽  
Injured Brain ◽  
Neurological Conditions ◽  
Characteristic Features ◽  
Mesodermal Lineage

Microgliosis is an intense reaction of CNS microglia to pathogenic insults. One of the characteristic features of microgliosis is an increase in the number of activated microglia at the site of lesion. Ontogenically, microglia are considered to be of mesodermal lineage in the adult CNS, but the origin of the accumulated microglia in pathological conditions remains controversial. Some studies indicate that circulating cells from the bloodstream can infiltrate the CNS and contribute to microglial pool, but some studies suggest that local expansion of reactive microglia is the sole source for parenchymal microglia. Recent data suggest that latent progenitors may also exist in the CNS. Available evidence suggests that multiple sources of microglia may exist under various neurological conditions. In this review, we compare the prevalent views and supporting evidence from different experimental models and provide an overview on the origins of microgliosis.

scholarly journals N region diversity of a transgenic substrate in fetal and adult lymphoid cells.

1992 ◽  
Vol 176 (5) ◽  
pp. 1399-1404 ◽  
Author(s):  
P Engler ◽  
E Klotz ◽  
U Storb
Keyword(s):  
Adult Mouse ◽  
Fetal Liver ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Single Pair ◽  
Stage Of Development ◽  
Fetal Stage ◽  
Test Gene ◽  
Complementarity Determining Region

The rearrangement of immunoglobulin (Ig) and T cell receptor (TCR) genes requires the activity of an as yet undefined V(D)J recombinase. One component of the recombinase appears to be a terminal transferase which may be involved in the addition of untemplated nucleotides (N regions) to the V(D)J joints. It has been observed that rearranged Ig and TCR genes isolated from fetal liver have few if any N regions, whereas in the adult mouse, these genes have a large number of untemplated nucleotides. The presence of N regions greatly alters the composition of the third hypervariable, complementarity determining region of the respective proteins, thus playing a major role in the conformation of the binding site. It was possible that, for functional reasons, N region-containing Ig and TCR genes were not permissible at the fetal stage of development. We have produced transgenic mice with a rearrangement test gene which, after V-J recombination, does not result in the production of functional Ig or TCR proteins. We report here that the rearrangement products have no N regions in fetal liver, but that the majority of joints in adult lymphoid tissues have N additions. The study is also an interesting demonstration of the randomness of rearrangements and the enormous variability that can be created from a single pair of V and J sequences.

Erythropoiesis from acetyl LDL incorporating endothelial cells at the preliver stage

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4733-4738 ◽  
Author(s):  
Daisuke Sugiyama ◽  
Minetaro Ogawa ◽  
Imiko Hirose ◽  
Thierry Jaffredo ◽  
Ken-ichi Arai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Colony Formation ◽  
Fetal Liver ◽  
White Blood Cells ◽  
Erythroid Cells ◽  
Whole Embryo Culture ◽  
Circulating Cells ◽  
Multipotent Progenitors ◽  
Labeling Method

AbstractErythropoiesis is characterized by 2 waves of production during mouse embryogenesis: a primitive one originating from the yolk sac (YS) and a definitive one produced from both the YS and the embryo proper. How the latter wave is generated remains unclear. To investigate our hypothesis that endothelial cells (ECs) could generate erythroid cells, we designed a method to label ECs at 10 days after coitus. This labeling method associates 2 techniques: an intracardiac inoculation that allows molecules to be delivered into the bloodstream followed by a whole-embryo culture period. DiI-conjugated acetylated low-density lipoproteins (Ac-LDL-DiI) were used to specifically tag ECs from the inside. One hour after inoculation, DiI staining was found along the entire endothelial tree. Fluorescence-activated cell sorter (FACS) analysis revealed that DiI+ cells were CD31+, CD34+, and CD45–, an antigen makeup characteristic of the endothelial lineage. Twelve hours after inoculation, 43% of DiI+ circulating cells belonged to the erythroid lineage. These cells expressed Ter119 and displayed an adult globin chain arrangement; thus they belonged to the definitive lineage as confirmed in erythroid colony formation. The remaining cells likely represent committed white blood cells or multipotent progenitors, as revealed by a mixed-colony formation. Beyond the 29-somite stage, the proportion of DiI+ erythroid cells gradually decreased. These results demonstrate the generation of hematopoietic cells from an endothelial intermediate, using in vivo tracing. We provide evidence for a release of these cells into the circulation and hypothesize that these cells are able to colonize the fetal liver and generate definitive erythrocytes in vivo.

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