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Given that chromosome and nuclear organization is tightly linked to biological state of the cell, the center will map the 4D nucleome for four key biological states representing different conformations during the cell cycle (interphase and mitosis), and during cell differentiation (pluripotent and differentiated states). We will obtain complementary data regarding the structure and dynamics of chromatin, at different length scales and in single cells using extensive high-throughput imaging, live cell imaging and super resolution microscopy. Data obtained with all approaches will be analyzed, integrated and modeled using a set of methods we will further develop to gain insights into the structure, physics and dynamics of chromosome folding over different length scales. Finally, a critical component of our proposal is the biological validation and further elaboration of the chromatin interaction maps that are generated from our conformational analyses. 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Furthermore, single-cell analysis reveals  independent behavior of individual alleles in single nuclei. Our observations  reveal extensive variability and heterogeneity in genome organization at the  level of individual alleles and demonstrate the coexistence of a broad spectrum  of genome configurations in a cell population.", "display_title": "Finn EH et al. 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