Person:
Torres, Miguel

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Miguel
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Torres
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CNIC
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2020 - 20245
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Author: Temiño, Susana ×

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Now showing 1 - 5 of 5
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    Cre recombinase microinjection for single-cell tracing and localised gene targeting.
    (The Company of Biologists, 2023-02-15) Sendra, Miquel; de Dios Hourcade, Juan; Temiño, Susana; Sarabia, Antonio J; Ocaña, Oscar H; Domínguez, Jorge N; Torres, Miguel; Ministerio de Ciencia e Innovación (España); Fundación La Caixa; Unión Europea. Comisión Europea. H2020; Centro Nacional de Investigaciones Cardiovasculares Carlos III (España)
    Tracing and manipulating cells in embryos are essential to understand development. Lipophilic dye microinjections, viral transfection and iontophoresis have been key to map the origin of the progenitor cells that form the different organs in the post-implantation mouse embryo. These techniques require advanced manipulation skills and only iontophoresis, a demanding approach of limited efficiency, has been used for single-cell labelling. Here, we perform lineage tracing and local gene ablation using cell-permeant Cre recombinase (TAT-Cre) microinjection. First, we map the fate of undifferentiated progenitors to the different heart chambers. Then, we achieve single-cell recombination by titrating the dose of TAT-Cre, which allows clonal analysis of nascent mesoderm progenitors. Finally, injecting TAT-Cre to Mycnflox/flox embryos in the primitive heart tube revealed that Mycn plays a cell-autonomous role in maintaining cardiomyocyte proliferation. This tool will help researchers identify the cell progenitors and gene networks involved in organ development, helping to understand the origin of congenital defects.
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    Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors.
    (Nature Publishing Group, 2021-05-25) Delgado, Irene; Giovinazzo, Giovanna; Temiño, Susana; Gauthier, Yves; Balsalobre, Aurelio; Drouin, Jacques; Torres, Miguel; Ministerio de Ciencia e Innovación (España); Fundación ProCNIC
    Meis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of Fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required for Shh activation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.
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    Pseudodynamic analysis of heart tube formation in the mouse reveals strong regional variability and early left–right asymmetry
    (Springer, 2022-05-16) Esteban, Isaac; Schmidt, Patrick; Desgrange, Audrey; Raiola, Morena; Temiño, Susana; Meilhac, Sigolène M.; Kobbelt, Leif; Torres, Miguel; Ministerio de Ciencia e Innovación (España); Agencia Estatal de Investigación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. H2020; Comunidad de Madrid (España); Ministerio de Economía y Competitividad (España); German Research Foundation; Institut Pasteur; Fundación ProCNIC; Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
    Understanding organ morphogenesis requires a precise geometrical description of the tissues involved in the process. The high morphological variability in mammalian embryos hinders the quantitative analysis of organogenesis. In particular, the study of early heart development in mammals remains a challenging problem due to imaging limitations and complexity. Here, we provide a complete morphological description of mammalian heart tube formation based on detailed imaging of a temporally dense collection of mouse embryonic hearts. We develop strategies for morphometric staging and quantification of local morphological variations between specimens. We identify hot spots of regionalized variability and identify Nodal-controlled left–right asymmetry of the inflow tracts as the earliest signs of organ left–right asymmetry in the mammalian embryo. Finally, we generate a three-dimensional+t digital model that allows co-representation of data from different sources and provides a framework for the computer modeling of heart tube formation
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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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    Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.
    (Nature Publishing Group, 2024-05-10) Li-Bao, Lin; Díaz-Díaz, Covadonga; Raiola, Morena; Sierra, Rocío; Temiño, Susana; Moya, Francisco J; Rodriguez-Perales, Sandra; Santos, Elisa; Giovinazzo, Giovanna; Bleckwehl, Tore; Rada-Iglesias, Álvaro; Spitz, Francois; Torres, Miguel; Agencia Estatal de Investigación (España); Unión Europea. Comisión Europea; Comunidad de Madrid (España); Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Fundación ProCNIC; Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
    MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.