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Single Cell Enhancer Activity Maps Neuronal Lineages in Embryonic Mouse Basal Ganglia

Linda Su-Feher, Anna N. Rubin, Shanni N. Silberberg, Rinaldo Catta-Preta, Kenneth J. Lim, Iva Zdilar, Christopher S. McGinnis, Gabriel L. McKinsey, Thomas E. Rubino Jr., Michael Hawrylycz, Carol Thompson, Zev J. Gartner, Luis Puelles, Hongkui Zeng, John L. R. Rubenstein, View ORCID ProfileAlex S. Nord
doi: https://doi.org/10.1101/2021.01.11.426285
Linda Su-Feher
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
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Anna N. Rubin
3Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, California, USA
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Shanni N. Silberberg
3Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, California, USA
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Rinaldo Catta-Preta
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
11Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA
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Kenneth J. Lim
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
3Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, California, USA
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Iva Zdilar
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
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Christopher S. McGinnis
4Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
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Gabriel L. McKinsey
5Department of Pediatrics, University of California, San Francisco, San Francisco, USA
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Thomas E. Rubino Jr.
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
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Michael Hawrylycz
6Allen Institute for Brain Science, Seattle, WA, USA
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Carol Thompson
6Allen Institute for Brain Science, Seattle, WA, USA
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Zev J. Gartner
4Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
7Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
8Chan Zuckerberg BioHub, University of California San Francisco, San Francisco, CA, USA
9Center for Cellular Construction, University of California San Francisco, San Francisco, CA, USA.
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Luis Puelles
10Department of Human Anatomy and Psychobiology and IMIB-Arrixaca Institute, University of Murcia, Spain
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Hongkui Zeng
6Allen Institute for Brain Science, Seattle, WA, USA
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John L. R. Rubenstein
3Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco Medical School, San Francisco, California, USA
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  • For correspondence: asnord@ucdavis.edu john.rubenstein@ucsf.edu
Alex S. Nord
1Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California, USA
2Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California, USA
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  • ORCID record for Alex S. Nord
  • For correspondence: asnord@ucdavis.edu john.rubenstein@ucsf.edu
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Abstract

Enhancers integrate transcription factor signaling pathways that drive cell fate specification in the developing brain. We used single cell RNA-sequencing (scRNA-seq) to capture enhancer activity at single cell resolution and delineate specification of cells labeled by enhancers in mouse medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) at embryonic day (E)11.5. We combine enhancer-based reporter labeling with single-cell transcriptional readout to characterize enhancer activity and define cell populations in vivo. Seven enhancers had diverse activities in specific progenitor and neuronal populations within the GEs. We then applied enhancer-based labeling, scRNA-seq, and analysis of in situ hybridization (ISH) data to distinguish subtypes of MGE-derived GABAergic and cholinergic projection neurons and interneurons. This work demonstrates how the power of scRNA-seq can be extended by enhancer-based labelling and leveraging ISH data and reveals novel lineage specification paths underlying patterning of developing mouse brain.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2021.
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Single Cell Enhancer Activity Maps Neuronal Lineages in Embryonic Mouse Basal Ganglia
Linda Su-Feher, Anna N. Rubin, Shanni N. Silberberg, Rinaldo Catta-Preta, Kenneth J. Lim, Iva Zdilar, Christopher S. McGinnis, Gabriel L. McKinsey, Thomas E. Rubino Jr., Michael Hawrylycz, Carol Thompson, Zev J. Gartner, Luis Puelles, Hongkui Zeng, John L. R. Rubenstein, Alex S. Nord
bioRxiv 2021.01.11.426285; doi: https://doi.org/10.1101/2021.01.11.426285
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Single Cell Enhancer Activity Maps Neuronal Lineages in Embryonic Mouse Basal Ganglia
Linda Su-Feher, Anna N. Rubin, Shanni N. Silberberg, Rinaldo Catta-Preta, Kenneth J. Lim, Iva Zdilar, Christopher S. McGinnis, Gabriel L. McKinsey, Thomas E. Rubino Jr., Michael Hawrylycz, Carol Thompson, Zev J. Gartner, Luis Puelles, Hongkui Zeng, John L. R. Rubenstein, Alex S. Nord
bioRxiv 2021.01.11.426285; doi: https://doi.org/10.1101/2021.01.11.426285

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