Person:
Lioux, Ghislaine

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Ghislaine
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Lioux
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CNIC
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2016 - 20203
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Now showing 1 - 3 of 3
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    Publication
    Retrospective clonal analysis of the developing mouse heart
    (2019-02-20) Lioux, Ghislaine; Torres, Miguel; Ministerio de Ciencia, Innovación y Universidades (España); Ministerio de Economía, Industria y Competitividad (España); Fundación ProCNIC; Fondation Leducq; Unión Europea. Comisión Europea
    The cardiac OFT is composed of endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts (Fbs) and Cardiomyocytes (CMs) known to derive from neural crest and second heart field (SHF) progenitors. The OFT is also covered by a mesothelial sheet of arterial mesothelial cells (AMCs) continuous with the epicardium. While the epicardium arises from the proepicardium, the early progenitor of AMCs is unknown. Using mesothelial and SHF related Cre lines we identified the origin of AMCs to be in the dorsal pharyngeal mesoderm. During a systematic analysis of cardiac lineages by random clonal labelling in developing mouse hearts, we found that AMCs shared a clonal relationship with cells of the great arteries. AMC clones were of different nature along the great arteries. On one hand, distal AMCs in both vessels were clonally related to Fbs, SMCs and ECs. On the other hand, the proximal AMCs of the Pulmonary artery (PA), were clonally related to Fbs, SMCs, CMs and lymphatic endothelial cells (LECs) of the ventral part of the heart. These clones however, were never found together with lymphatic clones of the dorsal part of the heart suggesting multiple origins for cardiac lymphatic vessels. Fate mapping of VEGFR3+ progenitors at different stages showed that whereas dorsal lymphatics derive from pre-existing lymphatic vessels, formation of ventral lymphatics involves the late recruitment of nonlymphatic cells. Using a range of SHF-specific Cre lines, we found that SHF-derived cells form ventral but not dorsal cardiac lymphatics. These observations suggest that SHF progenitors are recruited in the mesothelial-sub-mesothelial region of the PA. To test this hypothesis, we transplanted portions of PA mesothelial/sub-mesothelial layers from fluorescent donors into wild type E14.5 hearts. Donor tissue invaded the host myocardium, forming lymphatic vessels. The exploration of molecular cues involved in the formation of that niche showed that Raldh2 is downregulated at transcriptional and protein levels in proximal AMCs. Moreover, the loss of RA signalling in mesothelial cells resulted in immature lymphatic vessels while an excess of RA triggered lymphatic hyper-remodelling in the PA. These data show that part of the ventral lymphatics form by recruitment of SHF progenitors at a vasculogenic niche specified in a low Raldh2 environment at the base of the PA.
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    A Second Heart Field-Derived Vasculogenic Niche Contributes to Cardiac Lymphatics.
    (Elsevier, 2020-02-10) Lioux, Ghislaine; Liu, Xiaolei; Temiño, Susana; Oxendine, Michael; Ayala, Estefanía; Ortega, Sagrario; Kelly, Robert G; Oliver, Guillermo; Torres, Miguel; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Comunidad de Madrid (España); Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
    The mammalian heart contains multiple cell types that appear progressively during embryonic development. Advance in determining cardiac lineage diversification has often been limited by the unreliability of genetic tracers. Here we combine clonal analysis, genetic lineage tracing, tissue transplantation, and mutant characterization to investigate the lineage relationships between epicardium, arterial mesothelial cells (AMCs), and the coronary vasculature. We report a contribution of the second heart field (SHF) to a vasculogenic niche composed of AMCs and sub-mesothelial cells at the base of the pulmonary artery. Sub-mesothelial cells from this niche differentiate into lymphatic endothelial cells and, in close association with AMC-derived cells, contribute to and are essential for the development of ventral cardiac lymphatics. In addition, regionalized epicardial/mesothelial retinoic acid signaling regulates lymphangiogenesis, contributing to the niche properties. These results uncover a SHF vasculogenic contribution to coronary lymphatic development through a local niche at the base of the great arteries.
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    Publication
    Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population
    (Nature Publishing Group, 2016) Villa del Campo, Cristina; Lioux, Ghislaine; Carmona, Rita; Sierra, Rocio; Munoz-Chapuli, Ramon; Claveria, Cristina; Torres, Miguel; Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España); Regional Government of Andalusia (España); Instituto de Salud Carlos III; Fundación ProCNIC
    Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability.