PT - JOURNAL ARTICLE AU - Tsung-Li Liu AU - Srigokul Upadhyayula AU - Daniel E. Milkie AU - Ved Singh AU - Kai Wang AU - Ian A. Swinburne AU - Kishore R. Mosaliganti AU - Zach M. Collins AU - Tom W. Hiscock AU - Jamien Shea AU - Abraham Q. Kohrman AU - Taylor N. Medwig AU - Daphne Dambournet AU - Ryan Forster AU - Brian Cunniff AU - Yuan Ruan AU - Hanako Yashiro AU - Steffen Scholpp AU - Elliot M. Meyerowitz AU - Dirk Hockemeyer AU - David G. Drubin AU - Benjamin L. Martin AU - David Q. Matus AU - Minoru Koyama AU - Sean G. Megason AU - Tom Kirchhausen AU - Eric Betzig TI - Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms AID - 10.1101/243352 DP - 2018 Jan 01 TA - bioRxiv PG - 243352 4099 - http://biorxiv.org/content/early/2018/01/09/243352.short 4100 - http://biorxiv.org/content/early/2018/01/09/243352.full AB - 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 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 two-channel 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.One Sentence Summary Combining lattice light sheet microscopy with adaptive optics enables high speed, high resolution in vivo 3D imaging of dynamic processes inside cells under physiological conditions within their parent organisms.