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Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems.
Alon, Shahar; Goodwin, Daniel R; Sinha, Anubhav; Wassie, Asmamaw T; Chen, Fei; Daugharthy, Evan R; Bando, Yosuke; Kajita, Atsushi; Xue, Andrew G; Marrett, Karl; Prior, Robert; Cui, Yi; Payne, Andrew C; Yao, Chun-Chen; Suk, Ho-Jun; Wang, Ru; Yu, Chih-Chieh Jay; Tillberg, Paul; Reginato, Paul; Pak, Nikita; Liu, Songlei; Punthambaker, Sukanya; Iyer, Eswar P R; Kohman, Richie E; Miller, Jeremy A; Lein, Ed S; Lako, Ana; Cullen, Nicole; Rodig, Scott; Helvie, Karla; Abravanel, Daniel L; Wagle, Nikhil; Johnson, Bruce E; Klughammer, Johanna; Slyper, Michal; Waldman, Julia; Jané-Valbuena, Judit; Rozenblatt-Rosen, Orit; Regev, Aviv; Church, George M; Marblestone, Adam H; Boyden, Edward S.
Affiliation
  • Alon S; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Goodwin DR; McGovern Institute, MIT, Cambridge, MA, USA.
  • Sinha A; Faculty of Engineering, Gonda Brain Research Center and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
  • Wassie AT; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Chen F; McGovern Institute, MIT, Cambridge, MA, USA.
  • Daugharthy ER; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Bando Y; McGovern Institute, MIT, Cambridge, MA, USA.
  • Kajita A; Harvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA.
  • Xue AG; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Marrett K; McGovern Institute, MIT, Cambridge, MA, USA.
  • Prior R; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Cui Y; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Payne AC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Yao CC; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Suk HJ; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA.
  • Wang R; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Yu CJ; Kioxia Corporation, Minato-ku, Tokyo, Japan.
  • Tillberg P; Fixstars Solutions Inc, Irvine, CA, USA.
  • Reginato P; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Pak N; Fixstars Solutions Inc, Irvine, CA, USA.
  • Liu S; Fixstars Solutions Inc, Irvine, CA, USA.
  • Punthambaker S; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Iyer EPR; McGovern Institute, MIT, Cambridge, MA, USA.
  • Kohman RE; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Miller JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lein ES; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Lako A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cullen N; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Rodig S; McGovern Institute, MIT, Cambridge, MA, USA.
  • Helvie K; Harvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA.
  • Abravanel DL; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Wagle N; McGovern Institute, MIT, Cambridge, MA, USA.
  • Johnson BE; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Klughammer J; McGovern Institute, MIT, Cambridge, MA, USA.
  • Slyper M; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Waldman J; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Jané-Valbuena J; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Rozenblatt-Rosen O; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Church GM; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA.
  • Marblestone AH; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.
  • Boyden ES; McGovern Institute, MIT, Cambridge, MA, USA.
Science ; 371(6528)2021 01 29.
Article in En | MEDLINE | ID: mdl-33509999
ABSTRACT
Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq) to the mouse brain, which yielded the readout of thousands of genes, including splice variants. Targeted ExSeq yielded nanoscale-resolution maps of RNAs throughout dendrites and spines in the neurons of the mouse hippocampus, revealing patterns across multiple cell types, layer-specific cell types across the mouse visual cortex, and the organization and position-dependent states of tumor and immune cells in a human metastatic breast cancer biopsy. Thus, ExSeq enables highly multiplexed mapping of RNAs from nanoscale to system scale.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sequence Analysis, RNA / Gene Expression Profiling / Molecular Imaging / Single-Cell Analysis Limits: Animals / Female / Humans Language: En Journal: Science Year: 2021 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sequence Analysis, RNA / Gene Expression Profiling / Molecular Imaging / Single-Cell Analysis Limits: Animals / Female / Humans Language: En Journal: Science Year: 2021 Type: Article Affiliation country: United States