Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems.

Autor: Alon S; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Faculty of Engineering, Gonda Brain Research Center and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel., Goodwin DR; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA., Sinha A; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Harvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA., Wassie AT; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA., Chen F; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Daugharthy ER; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Bando Y; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; Kioxia Corporation, Minato-ku, Tokyo, Japan., Kajita A; Fixstars Solutions Inc, Irvine, CA, USA., Xue AG; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA., Marrett K; Fixstars Solutions Inc, Irvine, CA, USA., Prior R; Fixstars Solutions Inc, Irvine, CA, USA., Cui Y; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA., Payne AC; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Yao CC; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Suk HJ; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Harvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA., Wang R; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA., Yu CJ; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA., Tillberg P; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA., Reginato P; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Pak N; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA.; McGovern Institute, MIT, Cambridge, MA, USA.; Department of Mechanical Engineering, MIT, Cambridge, MA, USA., Liu S; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Punthambaker S; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Iyer EPR; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Kohman RE; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Miller JA; Allen Institute for Brain Science, Seattle, WA, USA., Lein ES; Allen Institute for Brain Science, Seattle, WA, USA., Lako A; Center for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA., Cullen N; Center for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA., Rodig S; Center for Immuno-Oncology (CIO), Dana-Farber Cancer Institute, Boston, MA, USA., Helvie K; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Abravanel DL; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Wagle N; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Johnson BE; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA., Klughammer J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Slyper M; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Waldman J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Jané-Valbuena J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Rozenblatt-Rosen O; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Regev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Church GM; Department of Genetics, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu edboyden@mit.edu.; Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA., Marblestone AH; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA., Boyden ES; Department of Media Arts and Sciences, MIT, Cambridge, MA, USA. gchurch@genetics.med.harvard.edu edboyden@mit.edu.; McGovern Institute, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA.; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Jan 29; Vol. 371 (6528).
DOI: 10.1126/science.aax2656
Abstrakt: 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.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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