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In the published publication [...].
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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.
Asunto(s)
Elementos de Facilitación Genéticos , Regulación del Desarrollo de la Expresión Génica , Células Madre Pluripotentes , Proteínas Proto-Oncogénicas c-myc , Animales , Ratones , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Transcripción Genética , Embrión de Mamíferos/metabolismo , Células Madre Embrionarias/metabolismo , Femenino , MasculinoRESUMEN
Heart morphogenesis is a complex and dynamic process that has captivated researchers for almost a century. This process involves three main stages, during which the heart undergoes growth and folding on itself to form its common chambered shape. However, imaging heart development presents significant challenges due to the rapid and dynamic changes in heart morphology. Researchers have used different model organisms and developed various imaging techniques to obtain high-resolution images of heart development. Advanced imaging techniques have allowed the integration of multiscale live imaging approaches with genetic labeling, enabling the quantitative analysis of cardiac morphogenesis. Here, we discuss the various imaging techniques used to obtain high-resolution images of whole-heart development. We also review the mathematical approaches used to quantify cardiac morphogenesis from 3D and 3D+time images and to model its dynamics at the tissue and cellular levels.
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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.