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      Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms.

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          Abstract

          True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          April 20 2018
          : 360
          : 6386
          Affiliations
          [1 ] Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
          [2 ] Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
          [3 ] Program in Cellular and Molecular Medicine, Boston Children's Hospital, 200 Longwood Avenue, Boston, MA 02115, USA.
          [4 ] Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
          [5 ] Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
          [6 ] Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
          [7 ] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
          [8 ] Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
          [9 ] Living Systems Institute, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK.
          [10 ] Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany.
          [11 ] Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. betzige@janelia.hhmi.org.
          Article
          360/6386/eaaq1392
          10.1126/science.aaq1392
          29674564

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