Biology subjects

Abizanda, G.

Publications and source records attributed to Abizanda, G..

4 recordsLinked to original sources

bioRxiv2024

Unravelling the molecular activation of the reparative cardiac fibroblasts after myocardial infarction

Activated cardiac fibroblasts (Postn+ CFs) are responsible for the healing of the heart tissue after a myocardial infarction (MI). However, so far little is known about the moment that CFs are activated, and the genes involved in this process. This is especially relevant in the context of CF heterogeneity and their role in the response to the damage. In this context, we have described a subpopulation of activated CFs responsible for the healing scar and for preventing the rupture of the ventricle after the damage: the Reparative Cardiac Fibroblasts (RCFs). Our new data indicate that RCFs directly derived from activated CFs, and this transcriptional shift happens in a close window after damage. Interestingly, our results exhibited two different molecular dynamics that would give rise to this activation and, consequently, the appearance of definitive RCFs. Using bulk RNA-Seq, RNAScope and Spatial Transcriptomics, we anatomically localized some of the genes related to both dynamics in the infarcted heart and highlight the potential role of Aspn as a new marker of this transcriptional transition in mice, pigs and patients.

bioinformatics↗

bioRxiv2022

In vivo generation of heart and vascular system by blastocyst complementation

The generation of organs from stem cells by blastocyst complementation is a promising approach to cover the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation we rescued heart and vascular development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs.

cell biology↗

bioRxiv2022

Revealing cell populations catching the early stages of the human embryo development in naive pluripotent stem cells

Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryos epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSCs (hiPSCs) cultures. Noteworthily these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represented the main cell population, interestingly we detected a cell population with gene and transposable element expression profile closely resembling the totipotent 8-Cell (8C) stage human embryo, and three cell populations analogous to trophectoderm (TE) cells at different stages of their maturation process: transition, early and mature stage. Thus, 5iLAF naive hiPSCs cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/482812v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@11b680eorg.highwire.dtl.DTLVardef@4c7e0forg.highwire.dtl.DTLVardef@1e84568org.highwire.dtl.DTLVardef@24ee65_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Single-cell RNA-seq analysis reveals the crucial role of Collagen Triplex Helix Repeat Containing 1 (CTHRC1) cardiac fibroblasts for ventricular remodeling after myocardial infarction

Cardiac fibroblasts have a central role during the ventricular remodeling process associated with different types of cardiac injury. Recent studies have shown that fibroblasts do not respond homogeneously to heart damage, suggesting that the adult myocardium may contain specialized fibroblast subgroups with specific functions. Due to the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population dynamics in response to cardiac damage is still missing. Using single-cell RNA-seq, we identified and characterized a fibroblast subpopulation that emerges in response to myocardial infarction (MI) in a murine model. These activated fibroblasts exhibit a clear pro-fibrotic signature, express high levels of the hormone CTHRC1 and of the immunomodulatory co-receptor CD200 and localize to the injured myocardium. Combining epigenomic profiling with functional assays, we show Sox9 and the non-canonical TGF-{beta} signaling as important regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, in this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture in a mouse model of myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig pre-clinical model of MI and establish a correlation between CTHRC1 levels and cardiac function after MI.

cell biology↗