Josselyn Sofia Vergara Cobos

All Publications

• A marmoset brain cell census reveals regional specialization of cellular identities SCIENCE ADVANCES Krienen, F. M., Levandowski, K. M., Zaniewski, H., del Rosario, R. H., Schroeder, M. E., Goldman, M., Wienisch, M., Lutservitz, A., Beja-Glasser, V. F., Chen, C., Zhang, Q., Chan, K. Y., Li, K. X., Sharma, J., Mccormack, D., Shin, T., Harrahill, A., Nyase, E., Mudhar, G., Mauermann, A., Wysoker, A., Nemesh, J., Kashin, S., Vergara, J., Chelini, G., Dimidschstein, J., Berretta, S., Deverman, B. E., Boyden, E., Mccarroll, S. A., Feng, G. 2023; 9 (41): eadk3986

  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.

  View details for DOI 10.1126/sciadv.adk3986

  View details for Web of Science ID 001086506900023

  View details for PubMedID 37824615

  View details for PubMedCentralID PMC10569717

• Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans NATURE NEUROSCIENCE Vormstein-Schneider, D., Lin, J. D., Pelkey, K. A., Chittajallu, R., Guo, B., Arias-Garcia, M. A., Allaway, K., Sakopoulos, S., Schneider, G., Stevenson, O., Vergara, J., Sharma, J., Zhang, Q., Franken, T. P., Smith, J., Ibrahim, L. A., Astro, K. M., Sabri, E., Huang, S., Favuzzi, E., Burbridge, T., Xu, Q., Guo, L., Vogel, I., Sanchez, V., Saldi, G. A., Gorissen, B. L., Yuan, X., Zaghloul, K. A., Devinsky, O., Sabatini, B. L., Batista-Brito, R., Reynolds, J., Feng, G., Fu, Z., McBain, C. J., Fishell, G., Dimidschstein, J. 2020; 23 (12): 1629-U221

  Abstract

  Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

  View details for DOI 10.1038/s41593-020-0692-9

  View details for Web of Science ID 000560308500002

  View details for PubMedID 32807948

  View details for PubMedCentralID PMC8015416