In situ genome sequencing resolves DNA sequence and structure in intact biological samples

Andrew C. Payne; Zachary D. Chiang; Paul L. Reginato; Sarah M. Mangiameli; Evan M. Murray; Chun-Chen Yao; Styliani Markoulaki; Andrew S. Earl; Ajay S. Labade; Rudolf Jaenisch; George M. Church; Edward S. Boyden; Jason D. Buenrostro; Fei Chen

doi:10.1126/science.aay3446

Research Article

In situ genome sequencing resolves DNA sequence and structure in intact biological samples

View ORCID ProfileAndrew C. Payne ¹,²,*,
View ORCID ProfileZachary D. Chiang ²,³,*,
View ORCID ProfilePaul L. Reginato ¹,²,⁴,⁵,⁶,*,
View ORCID ProfileSarah M. Mangiameli²,
Evan M. Murray²,
Chun-Chen Yao²,⁷,
View ORCID ProfileStyliani Markoulaki⁸,
View ORCID ProfileAndrew S. Earl³,
View ORCID ProfileAjay S. Labade³,
View ORCID ProfileRudolf Jaenisch⁸,⁹,
View ORCID ProfileGeorge M. Church⁵,⁶,
View ORCID ProfileEdward S. Boyden¹,⁴,⁷,¹⁰,¹¹,¹²,¹³,†,‡,
View ORCID ProfileJason D. Buenrostro ²,³,†,‡,
View ORCID ProfileFei Chen ²,³,†,‡

¹Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
²Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
³Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
⁴Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
⁵Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
⁶Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁷Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
⁸Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
⁹Department of Biology, MIT, Cambridge, MA 02139, USA.
¹⁰McGovern Institute, MIT, Cambridge, MA 02139, USA.
¹¹Koch Institute, MIT, Cambridge, MA 02139, USA.
¹²Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
¹³Centers for Neurobiological Engineering and Extreme Bionics, MIT, Cambridge, MA 02139, USA.

↵‡Corresponding author. Email: edboyden{at}mit.edu (E.S.B.); jason_buenrostro{at}harvard.edu (J.D.B.); chenf{at}broadinstitute.org (F.C.)

↵* These authors contributed equally to this work.
↵† These authors contributed equally to this work.

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Science 26 Feb 2021:
Vol. 371, Issue 6532, eaay3446
DOI: 10.1126/science.aay3446

Andrew C. Payne

1Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

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Zachary D. Chiang

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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Paul L. Reginato

1Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

4Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.

5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

6Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

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Sarah M. Mangiameli

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

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Evan M. Murray

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

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Chun-Chen Yao

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

7Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.

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Styliani Markoulaki

8Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.

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Andrew S. Earl

3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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Ajay S. Labade

3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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Rudolf Jaenisch

8Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.

9Department of Biology, MIT, Cambridge, MA 02139, USA.

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George M. Church

5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

6Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

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Edward S. Boyden

1Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

4Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.

7Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.

10McGovern Institute, MIT, Cambridge, MA 02139, USA.

11Koch Institute, MIT, Cambridge, MA 02139, USA.

12Howard Hughes Medical Institute, Cambridge, MA 02139, USA.

13Centers for Neurobiological Engineering and Extreme Bionics, MIT, Cambridge, MA 02139, USA.

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For correspondence: edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org

Jason D. Buenrostro

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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For correspondence: edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org

Fei Chen

2Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.

3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

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For correspondence: edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org

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In situ genome sequencing resolves DNA sequence and structure in intact biological samples

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