A marmoset brain cell census reveals regional specialization of cellular identities

Author:

Krienen Fenna M.12ORCID,Levandowski Kirsten M.234ORCID,Zaniewski Heather234ORCID,del Rosario Ricardo C.H.12,Schroeder Margaret E.234ORCID,Goldman Melissa12,Wienisch Martin234ORCID,Lutservitz Alyssa1,Beja-Glasser Victoria F.234,Chen Cindy234ORCID,Zhang Qiangge234ORCID,Chan Ken Y.2,Li Katelyn X.34ORCID,Sharma Jitendra34,McCormack Dana234ORCID,Shin Tay Won345ORCID,Harrahill Andrew34ORCID,Nyase Eric34,Mudhar Gagandeep6,Mauermann Abigail345,Wysoker Alec2,Nemesh James2,Kashin Seva2,Vergara Josselyn2ORCID,Chelini Gabriele7ORCID,Dimidschstein Jordane2,Berretta Sabina89ORCID,Deverman Benjamin E.2ORCID,Boyden Ed345ORCID,McCarroll Steven A.12ORCID,Feng Guoping23

Affiliation:

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

2. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

4. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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

6. Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA.

7. Center for Mind/Brain Sciences, University of Trento, Piazza della Manifattura n.1, Rovereto (TN) 38068, Italy.

8. Basic Neuroscience Division, McLean Hospital, Belmont, MA 02478, USA.

9. Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.

Abstract

The mammalian brain is composed of many brain structures, each with its own ontogenetic and developmental history. We used single-nucleus RNA sequencing to sample over 2.4 million brain cells across 18 locations in the common marmoset, a New World monkey primed for genetic engineering, and examined gene expression patterns of cell types within and across brain structures. The adult transcriptomic identity of most neuronal types is shaped more by developmental origin than by neurotransmitter signaling repertoire. Quantitative mapping of GABAergic types with single-molecule FISH (smFISH) reveals that interneurons in the striatum and neocortex follow distinct spatial principles, and that lateral prefrontal and other higher-order cortical association areas are distinguished by high proportions of VIP + neurons. We use cell type–specific enhancers to drive AAV-GFP and reconstruct the morphologies of molecularly resolved interneuron types in neocortex and striatum. Our analyses highlight how lineage, local context, and functional class contribute to the transcriptional identity and biodistribution of primate brain cell types.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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