Aranguren-López, X. (Xabier)

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    Revealing Cell Populations Catching The Early Stages Of Human Embryo Development In Naive Pluripotent Stem Cell Cultures
    (2023) Ullate-Agote, A. (Asier); Rodriguez-Madoz, J.R. (Juan Roberto); Garate-Iturriagagoitia, L. (Leire); Aranguren-López, X. (Xabier); Barreda, C. (Carolina); Coppiello, G. (Giulia); Romero-Riojas, J.P. (Juan Pablo); Carvajal-Vergara, X. (Xonia); Aguirre-Ena, X. (Xabier); Dupéré-Richer, D. (Daphné); Prosper, F. (Felipe); Moya-Jódar, M. (Marta); Barlabé-Ginesta, P. (Paula); Abizanda-Sarasa, G. (Gloria)
    Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo's 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 PSC (hiPSC) cultures. It is noteworthy that these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represent the main cell population, interestingly we detect a cell population with gene and transposable element expression profile closely resembling the totipotent eight-cell (8C)-stage human embryo, and three cell populations analogous to trophectoderm cells at different stages of their maturation process: transition, early, and mature stages. Moreover, we reveal the presence of cells resembling primitive endoderm. Thus, 5iLAF naive hiPSC cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.
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    Generation of heart and vascular system in rodents by blastocyst complementation
    (2023) Ullate-Agote, A. (Asier); Abizanda-Sarasa, G. (Gloria María); Aranguren-López, X. (Xabier); San-Martín-Uriz, P. (Patxi); Barreda, C. (Carolina); Coppiello, G. (Giulia); Larequi-Ardanaz, E. (Eduardo); Carvajal-Vergara, X. (Xonia); Pelacho-Samper, B. (Beatriz); Ruiz-Villalba, A. (Adrián); Mazo, M. (Manuel); Arellano-Viera, E. (Estíbaliz); Pérez-Pomares, J.M. (José María); Linares, J. (Javier); Pogontke, C. (Cristina); Iglesias, E. (Elena); Prosper-Cardoso, F. (Felipe); Moya-Jódar, M. (Marta); Barlabé-Ginesta, P. (Paula)
    Generating organs from stem cells through blastocyst complementation is a promising approach to meet 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 system 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 invivo generation of transplantable organs.