physiopathology of development

Congenital heart diseases (CHD) are the most frequent congenital diseases. GWAS  and exome sequencing performed for the last decade revealed mutations in coding sequence in only a minority of CHD patients. Rather a high proportion of hits in epigenetic modifiers was found. Thus, the team physiopathology of cardiac development focuses its research on epigenetic regulation of cell fate determination during cardiac embryonic development. We are specifically focused on Tetralogy of Fallot and valve development and diseases, as they represent altogether 50% of cardiac congenital defects. These pathologies either lead to heart failure at the adulthood or become prominent in the aging population, respectively. Our research is also dedicated to better design strategies of cell therapy of heart failure for repaired tetralogy of Fallot, a complex cardiac congenital disease, for which reparation of the septal defect at birth has consequences on adult right ventricular function. To more specifically address such a broad biological question, we carry out different projects using patient specific iPS cell lines and mouse models of diseases:

  1. The Cornelia de Lange syndrome:  what are the epigenetic mechanisms underlying this cohesinopathy? What is the role of cohesin complex in cardiac cell fate decision? Thomas Moore-Morris and Fanny Boulet in collaboration with Valérie Cormier-Daire (Imagine Institute , Paris)
  2. Cell fate determination during cardiac valvulogenesis: a clonal analysis combined with a single cell-sequencing approaches: from development to diseases Batoul Fahrat
  3. The laminopathy at the origin of a cardiomyopathy: a congenital disease with an epigenetic origin: postdoc to be recruited in collaboration with Gisèle Bonne Institute of Myology (Institut de myologie, Paris)
  4. The role of epigenetics in vitamin D deficiency and CHD: Eva Siepelt in collaboration with Jean-Francois Landrier (Nort Univ AMU)
  5. Cardiac Regeneration in a pig model of cardiac congenital disease : Virginie Lambert  in collaboration with the pediatric cardiology service La timone Hospital ( Service médico-chirurgical de cardiologie pédiatrique et congénitale - Hôpital de la Timone) and CERIMED (CERIMED)

The head of the team Michel Puceat is an INSERM director of research. He has signed more than 110 publications. He has acquired a background of cardiac biochemistry and physiology as well as cardiac developmental biology.

Sturny, R.  et al. 2016

FGF10 is required to promote cardiomyocyte proliferation after myocardial infarction

WOS:000379812500009
Cardiovasc. Res. - issue: - volume: 111 - pages: S3-S3.

Rampersad, SN.  et al. 2016

Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear stress-encoded signals: modulation by phosphodiesterase 4D-VE-cadherin signalling

Although cAMP-signalling regulates numerous functions of vascular endothelial cells (VECs), including their ability to impact vascular resistance in response to changes in blood flow dynamics, few of...
Cell. Signal. - issue: 7 - volume: 28 - pages: 741-748.

Rampersad, SN.  et al. 2016

EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction

Blood flow-associated fluid shear stress (FSS) dynamically regulates the endothelium's ability to control arterial structure and function. While arterial endothelial cells (AEC) subjected to high...
Cell. Signal. - issue: 6 - volume: 28 - pages: 606-619.

Smith, PM.  et al. 2016

Leptin influences the excitability of area postrema neurons

The area postrema (AP) is a circumventricular organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggested...
Am. J. Physiol.-Regul. Integr. Comp. Physiol. - issue: 5 - volume: 310 - pages: R440-R448.

Durst, R.  et al. 2015

Mutations in DCHS1 cause mitral valve prolapse

Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals(1-3). It can manifest as mitral regurgitation and is the leading indication for mitral valve...
Nature - issue: 7567 - volume: 525 - pages: 109-+.

Moore-Morris, T.  et al. 2015

Cardiac fibroblasts: from development to heart failure

Cardiac fibroblasts are a major cell population of the heart and are characterized by their capacity to produce extracellular matrix (ECM). In hearts subjected to pressure overload, excessive...
J. Mol. Med. - issue: 8 - volume: 93 - pages: 823-830.

Leschik, J.  et al. 2015

A View of Bivalent Epigenetic Marks in Two Human Embryonic Stem Cell Lines Reveals a Different Cardiogenic Potential

Human embryonic stem (HUES) cells are derived from early individual embryos with unique genetic printing. However, how their epigenetic status might affect their potential to differentiate toward...
Stem Cells Dev. - issue: 3 - volume: 24 - pages: 384-392.

Ahles, A.  et al. 2015

Interhelical Interaction and Receptor Phosphorylation Regulate the Activation Kinetics of Different Human beta(1)-Adrenoceptor Variants

G protein-coupled receptors represent the largest class of drug targets, but genetic variation within G protein-coupled receptors leads to variable drug responses and, thereby, compromises their...
J. Biol. Chem. - issue: 3 - volume: 290 - pages: 1760-1769.

Hamdi, H.  et al. 2014

Long-Term Functional Benefits of Epicardial Patches as Cell Carriers

Both enzymatic dissociation of cells prior to needle-based injections and poor vascularization of myocardial infarct areas are two important contributors to cell death and impede the efficacy of...
Cell Transplant. - issue: 1 - volume: 23 - pages: 87-96.

Rochais, F.  et al. 2014

FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry

Aims Cardiomyocyte proliferation gradually declines during embryogenesis resulting in severely limited regenerative capacities in the adult heart. Understanding the developmental processes controlling...
Cardiovasc. Res. - issue: 3 - volume: 104 - pages: 432-442.

Richart, A.  et al. 2014

MicroRNA-21 Coordinates Human Multipotent Cardiovascular Progenitors Therapeutic Potential

Published clinical trials in patients with ischemic diseases show limited benefit of adult stem cell-based therapy, likely due to their restricted plasticity and commitment toward vascular cell...
Stem Cells - issue: 11 - volume: 32 - pages: 2908-2922.

Sussman, MA.  et al. 2014

Response to Letter Regarding Article, "Embryonic Stem Cell-Derived Cardiac Myocytes Are Not Ready for Human Trials"

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Circ.Res. - issue: 10 - volume: 115 - pages: E30-E31.

Moore-Morris, T.  et al. 2014

Targeting cardiac fibroblasts: The pressure is on

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Cell Cycle - issue: 17 - volume: 13 - pages: 2647-2648.

Anderson, ME.  et al. 2014

Embryonic Stem Cell-Derived Cardiac Myocytes Are Not Ready for Human Trials

WOS:000339272700004
Circ.Res. - issue: 3 - volume: 115 - pages: 335-338.

Rochais, F.  et al. 2014

FGF10 regulates regional proliferation in the fetal heart through a FOXO3/p27kip1 pathway and promotes cell cycle reentry of adult cardiomyocytes

WOS:000343730100241
Cardiovasc. Res. - issue: - volume: 103 - pages: .

Maurice, DH.  et al. 2014

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that...
Biochem. Soc. Trans. - issue: - volume: 42 - pages: 250-256.

Hiriart, E.  et al. 2014

Cell Labeling and Injection in Developing Embryonic Mouse Hearts

Testing the fate of embryonic or pluripotent stem cell-derivatives in in vitro protocols has led to controversial outcomes that do not necessarily reflect their in vivo potential. Preferably, these...
J. Vis. Exp. - issue: 86 - volume: - pages: e51356.

Maurice, DH.  et al. 2014

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that...
Biochem. Soc. Trans. - issue: - volume: 42 - pages: 250-256.

Ahles, A.  et al. 2014

The Arg389Gly polymorphism determines structure and activation kinetics of the human beta(1)-adrenergic receptor

WOS:000359538500093
Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 387 - pages: S24-S24.

Puceat, M.  et al. 2013

Could a pluripotent stem cell give rise to a high yield of a single cell lineage: a myocardial cell?

WOS:000324362900019
Curr. Opin. Genet. Dev. - issue: 4 - volume: 23 - pages: 498-499.

Catelain, C.  et al. 2013

Myoblasts and Embryonic Stem Cells Differentially Engraft in a Mouse Model of Genetic Dilated Cardiomyopathy

The functional and architectural benefits of embryonic stem cells (ESC) and myoblasts (Mb) transplantations into infarcted myocardium have been investigated extensively. Whereas ESC repopulated...
Mol. Ther. - issue: 5 - volume: 21 - pages: 1064-1075.

Puceat, M.  et al. 2013

Embryological origin of the endocardium and derived valve progenitor cells: From developmental biology to stem cell-based valve repair

The cardiac valves are targets of both congenital and acquired diseases. The formation of valves during embryogenesis (i.e., valvulogenesis) originates from endocardial cells lining the myocardium....
Biochim. Biophys. Acta-Mol. Cell Res. - issue: 4 - volume: 1833 - pages: 917-922.

Ahles, A.  et al. 2013

Phosphorylation-dependent receptor memory of the human beta(1)-adrenergic receptor

WOS:000209476400005
Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 386 - pages: S3-S3.

Van Vliet, P.  et al. 2012

Early cardiac development: a view from stem cells to embryos

From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the...
Cardiovasc. Res. - issue: 3 - volume: 96 - pages: 352-362.

Zhai, K.  et al. 2012

beta-Adrenergic cAMP Signals Are Predominantly Regulated by Phosphodiesterase Type 4 in Cultured Adult Rat Aortic Smooth Muscle Cells

Background: We investigated the role of cyclic nucleotide phosphodiesterases (PDEs) in the spatiotemporal control of intracellular cAMP concentrations in rat aortic smooth muscle cells (RASMCs)....
PLoS One - issue: 10 - volume: 7 - pages: e47826.

Calderon, D.  et al. 2012

Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells

Transplantation of allogeneic human embryonic stem cell-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of...
J. Cell. Mol. Med. - issue: 7 - volume: 16 - pages: 1544-1552.

Boon, R.  et al. 2012

A Day in the Life of a Young Investigator

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Circulation - issue: 25 - volume: 125 - pages: F145-F150.

Rochais, F.  et al. 2012

Fgf10 regulates fetal cardiac growth

WOS:000301975800412
Cardiovasc. Res. - issue: - volume: 93 - pages: S97-S97.

Ahles, A.  et al. 2012

The Gly389Arg polymorphism determines the activation kinetics of the human beta(1)-adrenergic receptor

WOS:000300779500007
Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 385 - pages: 4-4.

Goebel, P.  et al. 2012

Identification of novel targets of beta-adrenergic signaling through phosphoproteomics of the heart in vivo

WOS:000300779500124
Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 385 - pages: 29-30.

Paris, M.  et al. 2012

Regulation of skin aging and heart development by TAp63

Since the discovery of the TP63 gene in 1998, many studies have demonstrated that Delta Np63, a p63 isoform of the p53 gene family, is involved in multiple functions during skin development and in...
Cell Death Differ. - issue: 2 - volume: 19 - pages: 186-193.