Biology subjects

MARTIN, A.

Publications and source records attributed to MARTIN, A..

3 recordsLinked to original sources

bioRxiv2025

Accumulation of ph1 (zip4-5B) and ph2 (msh7-3D) mutations fails to boost homoeologous recombination in hexaploid wheat

Diversification of the hexaploid (bread) wheat genetic pool using wild genetic resources relies on effective meiotic recombination (crossover) between wheat chromosomes and their counterparts from related species (homoeologues). However, crossover between homoeologues is normally suppressed by two major genes, ZIP4-5B (Ph1) and MSH7-3D (Ph2). We investigated the effect of introducing zip4-5B and/or msh7-3D mutations into interspecific hybrids derived from crosses between wheat and Aegilops variabilis. Single and double mutants were exploited in Chinese Spring (CS) and Cadenza (Cad) genetic backgrounds, as well as in a CS/Cad recombinant background. The number of univalents, bivalents and multivalents was scored from meiotic cells at metaphase I, from which numbers of chiasmata were deduced. We demonstrated a non-cumulative effect of simultaneous zip4-5B and msh7-3D mutations on homoeologous recombination, as homoeologous crossovers reached a maximum when ZIP4-5B alone was mutated. We also showed that hybrids carrying both the zip4-5B and msh7-3D mutations in the same genetic background exhibited more effective recombination compared to a double mutant in the CS/Cad recombinant background. The progression of meiosis was also monitored in the different interspecific hybrids mutants, revealing clear disruptions. Thus, our study significantly contributes to the optimization of the introgression of beneficial alleles from wild relatives into elite wheat germplasm; first by demonstrating the efficiency of ZIP4-5B and MSH7-3D mutations independently and in combination and second by elucidating the influence of the genetic background in which these mutations are present in an interspecific hybrid context.

genetics↗

bioRxiv2024

LSD1 demethylase inhibition prevents cardiac fibrosis in both ischemic and congenital diseases in mice and pig models

Fibrosis is part of a clinical burden in cardiovascular diseases. The pathological process has been the subject of intensive research with still mitigated therapeutic options. Recently chromatin modifiers have turned out to be potential drugs to modulate fibrosis. Here, in order to address the question of pharmacological inhibition of fibrosis, we used both a mouse model of myocardial infarction with left ventricular fibrosis and a more clinically relevant pig model of right ventricular failure featuring interstitial fibrosis. Treatment of these diseased animal models with an inhibitor of the Lysine Demethylase 1 (LSD1) significantly prevented both left and right ventricular failure in both the mouse and the pig, respectively. This was revealed by a significant recovery of left ventricular function post-myocardial infarction in the mouse and a limitation of remodeling of the pig right ventricle, thus preserving its function. Fibrosis was significantly decreased in both mouse and pig hearts, which likely account for improvement in ventricular function. We thus provide evidence of the beneficial effect of LSD1 inhibitors in cardiac fibrosis and of the use of such drugs to preserve ventricular function in both ischemic and congenital heart diseases. NEW & NOTEWORTHYDrugs to prevent cardiac fibrosis has been the subject of intensive research with limited outcomes. This work inspired by oncology, provides evidence that an epigenetic modifier which targets the process of epithelial-to-mesenchymal transition turns out to be an efficient inhibitor of fibrosis for both ischemic and non-ischemic myocardial diseases.

pharmacology and toxicology↗

bioRxiv2022

Graft of cardiac progenitors in a pig model of right ventricular failure triggers myocardial epimorphosis, regeneration and protection of function

Heart left or right ventricular failure results from either ischemic or congenital diseases, respectively, and remains a major health burden in our societies. There is thus a high demand for a regenerative therapy. Yet, the ability of the adult post-mitotic mammalian heart to self-regenerate remains largely a challenge Here, we combined cell therapy in a pig with right heart failure, cardiac physiology, single cell RNA-seq and spatial transcriptomics. We demonstrate that resident cardiac macrophages mediate a process of cardiomyocytes de-differentiation to form a blastema which produces new proliferative cardiomyocytes. Thus, a mammalian heart close to a human heart features the ability to undergo epimorphosis and to regenerate. A direct and specific target of resident macrophages holds promise to regenerate hearts, specifically in a growing population of now adult congenital heart diseases patients with right ventricular failure and left without any efficient pharmacological relieving treatment.

developmental biology↗