scholarly journals HSA+ immature cardiomyocytes persist in the adult heart and expand after ischemic injury

2019 ◽  
Author(s):  
Mariana Valente ◽  
Tatiana Pinho Resende ◽  
Diana Santos Nascimento ◽  
Odile Burlen-Defranoux ◽  
Benoit Dupont ◽  
...  
Keyword(s):  
Cell Surface ◽  
Developmental Stage ◽  
Cardiac Tissue ◽  
Transcriptional Profiling ◽  
Surface Marker ◽  
Regenerative Capacity ◽  
Adult Heart ◽  
Adult Cardiomyocytes ◽  
Surface Marker Analysis

AbstractThe assessment of the regenerative capacity of the heart has been compromised by the lack of surface signatures to characterize cardiomyocytes. Here, combined multiparametric surface marker analysis with single cell transcriptional profiling and in vivo transplantation, identify the main fetal cardiac populations and their progenitors. We found that cardiomyocytes at different stages of differentiation co-exist during development. We identified a population of immature HSA/CD24+ cardiomyocytes that persists throughout life and that, unlike other cardiomyocyte subsets, actively proliferates up to one week of age and engraft cardiac tissue upon transplantation. In adult heart HSA/CD24+ cardiomyocytes appear as mononucleated cells that cycle and increase in frequency after infarction. Our work identified cell surface signatures that allow the prospective isolation of cardiomyocytes at any developmental stage and the detection of adult cardiomyocytes poised for activation in response to ischemic stimuli. This work opens new perspectives in the understanding and treatment of heart pathologies.

scholarly journals β-Catenin drives distinct transcriptional networks in proliferative and nonproliferative cardiomyocytes

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev193417
Author(s):  
Gregory A. Quaife-Ryan ◽  
Richard J. Mills ◽  
George Lavers ◽  
Holly K. Voges ◽  
Celine J. Vivien ◽  
...  
Keyword(s):  
Developmental Process ◽  
Transcriptional Profiling ◽  
Neonatal Mouse ◽  
Transcriptional Networks ◽  
Cardiomyocyte Proliferation ◽  
Regenerative Capacity ◽  
Adult Heart ◽  
Glycolytic Gene

ABSTRACTThe inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. By contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms for the developmental loss of cardiac regenerative capacity in mammals are not fully understood. Wnt/β-catenin signalling has been proposed as a key cardioregenerative pathway driving cardiomyocyte proliferation. Here, we show that Wnt/β-catenin signalling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. By contrast, Wnt/β-catenin signalling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling and chromatin immunoprecipitation sequencing of neonatal mouse and hPSC-CMs revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. By contrast, β-catenin failed to re-engage this neonatal proliferative gene network in the adult heart despite partial transcriptional re-activation of a neonatal glycolytic gene programme. These findings suggest that β-catenin might be repurposed from regenerative to protective functions in the adult heart in a developmental process dependent on the metabolic status of cardiomyocytes.

scholarly journals Epha1 is a cell surface marker for neuromesodermal progenitors and their early mesoderm derivatives

2019 ◽  
Author(s):  
Luisa de Lemos ◽  
André Dias ◽  
Ana Nóvoa ◽  
Moisés Mallo
Keyword(s):  
Cell Surface ◽  
Transcriptional Profiling ◽  
Surface Marker ◽  
Cell Surface Marker ◽  
Paraxial Mesoderm ◽  
Molecular Signature ◽  
Tail Bud ◽  
Molecular Fingerprint ◽  
Simple Method ◽  
Cell Subpopulations

ABSTRACTThe vertebrate body is built during embryonic development by the sequential addition of new tissue as the embryo grows at its caudal end. During this process, the neuro-mesodermal progenitors (NMPs) generate the postcranial neural tube and paraxial mesoderm. Recently, several approaches have been designed to determine their molecular fingerprint but a simple method to isolate NMPs from embryos without the need for transgenic markers is still missing. We isolated NMPs using a genetic strategy that exploits their self-renew properties, and searched their transcriptome for cell surface markers. We found a distinct Epha1 expression profile in progenitor-containing areas of the mouse embryo, consisting of two cell subpopulations with different Epha1 expression levels. We show that Sox2+/T+ cells are preferentially associated with the Epha1 compartment, indicating that NMPs might be contained within this cell pool. Transcriptional profiling showed enrichment of high Epha1-expressing cells in known NMP and early mesoderm markers. Also, tail bud cells with lower Epha1 levels contained a molecular signature suggesting the presence of notochord progenitors. Our results thus indicate that Epha1 could represent a valuable cell surface marker for different subsets of axial progenitors, most particularly for NMPs taking mesodermal fates.

Cytogenetics and cell surface marker analysis in CML — 1. Prediction of phenotype of acute phase transformation

1985 ◽  
Vol 9 (9) ◽  
pp. 1093-1098 ◽  
Author(s):  
Frances S. Ligler ◽  
Isadore Brodsky ◽  
Mark L. Schlam ◽  
Kathryn E. Fuscaldo
Keyword(s):  
Phase Transformation ◽  
Cell Surface ◽  
Acute Phase ◽  
Surface Marker ◽  
Cell Surface Marker ◽  
Marker Analysis ◽  
Surface Marker Analysis

scholarly journals Positive Feedback Regulation Between Adiponectin and T-Cadherin Impacts Adiponectin Levels in Tissue and Plasma of Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 934-946 ◽  
Author(s):  
Keisuke Matsuda ◽  
Yuya Fujishima ◽  
Norikazu Maeda ◽  
Takuya Mori ◽  
Ayumu Hirata ◽  
...  
Keyword(s):  
Cell Surface ◽  
Phospholipase C ◽  
Positive Feedback ◽  
Cardiac Tissue ◽  
Feedback Regulation ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Cleavage Enzyme ◽  
In Vivo Administration

Abstract Adiponectin (Adipo), a multimeric adipocyte-secreted protein abundant in the circulation, is implicated in cardiovascular protective functions. Recent work documented that Adipo locally associates with responsive tissues through interactions with T-cadherin (Tcad), an atypical, glycosylphosphatidylinositol (GPI)-anchored cadherin cell surface glycoprotein. Mice deficient for Tcad lack tissue-associated Adipo, accumulate Adipo in the circulation, and mimic the Adipo knockout (KO) cardiovascular phenotype. In reverse, Tcad protein is visibly reduced from cardiac tissue in Adipo-KO mice, suggesting interdependent regulation of the 2 proteins. Here, we evaluate the effect of Adipo on Tcad protein expression. Adipo and Tcad proteins were colocalized in aorta, heart, and skeletal muscle. Adipo positively regulated levels of Tcad protein in vivo and in endothelial cell (EC) cultures. In Tcad-KO mice, binding of endogenous and exogenously administered Adipo to cardiovascular tissues was dramatically reduced. Consistently, knockdown of Tcad in cultured murine vascular ECs significantly diminished Adipo binding. In search for a possible mechanism, we found that enzymatic cleavage of Tcad with phosphatidylinositol-specific phospholipase C increases plasma Adipo while decreasing tissue-bound levels. Similarly, pretreatment of cultured ECs with serum containing Adipo attenuated phosphatidylinositol-specific phospholipase C-mediated Tcad cleavage. In vivo administration of adenovirus producing Adipo suppressed plasma levels of GPI phospholipase D, the endogenous cleavage enzyme for GPI-anchored proteins. In conclusion, our data show that both circulating and tissue-bound Adipo levels are dependent on Tcad and, in reverse, regulate tissue Tcad levels through a positive feedback loop that operates by suppressing phospholipase-mediated Tcad release from the cell surface.

Acute dexamethasone-induced increase in cardiac lipoprotein lipase requires activation of both Akt and stress kinases

2008 ◽  
Vol 295 (1) ◽  
pp. E137-E147 ◽  
Author(s):  
Girish Kewalramani ◽  
Prasanth Puthanveetil ◽  
Min Suk Kim ◽  
Fang Wang ◽  
Vivian Lee ◽  
...  
Keyword(s):  
Cell Surface ◽  
Lipoprotein Lipase ◽  
P38 Mapk ◽  
Actin Polymerization ◽  
Cardiac Tissue ◽  
Whole Body ◽  
Isolated Cardiomyocytes ◽  
Stress Kinases ◽  
Cardiac Energy

Following dexamethasone (DEX), cardiac energy generation is mainly through utilization of fatty acids (FA), with DEX animals demonstrating an increase in coronary lipoprotein lipase (LPL), an enzyme that hydrolyzes lipoproteins to FA. We examined the mechanisms by which DEX augments cardiac LPL. DEX was injected in rats, and hearts were removed, or isolated cardiomyocytes were incubated with DEX (0–8 h), for measurement of LPL activity and Western blotting. Acute DEX induced whole body insulin resistance, likely an outcome of a decrease in insulin signaling in skeletal muscle, but not cardiac tissue. The increase in luminal LPL activity after DEX was preceded by rapid nongenomic alterations, which included phosphorylation of AMPK and p38 MAPK, that led to phosphorylation of heat shock protein (HSP)25 and actin cytoskeleton rearrangement, facilitating LPL translocation to the myocyte cell surface. Unlike its effects in vivo, although DEX activated AMPK and p38 MAPK in cardiomyocytes, there was no phosphorylation of HSP25, nor was there any evidence of F-actin polymerization or an augmentation of LPL activity up to 8 h after DEX. Combining DEX with insulin appreciably enhanced cardiomyocyte LPL activity, which closely mirrored a robust elevation in phosphorylation of HSP25 and F-actin polymerization. Silencing of p38 MAPK, inhibition of PI 3-kinase, or preincubation with cytochalasin D prevented the increases in LPL activity. Our data suggest that, following DEX, it is a novel, rapid, nongenomic phosphorylation of stress kinases that, together with insulin, facilitates LPL translocation to the myocyte cell surface.

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