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Single cell enhancer activity distinguishes GABAergic and cholinergic lineages in embryonic mouse basal ganglia
- Su-Feher, Linda;
- Rubin, Anna N;
- Silberberg, Shanni N;
- Catta-Preta, Rinaldo;
- Lim, Kenneth J;
- Ypsilanti, Athena R;
- Zdilar, Iva;
- McGinnis, Christopher S;
- McKinsey, Gabriel L;
- Rubino, Thomas E;
- Hawrylycz, Michael J;
- Thompson, Carol;
- Gartner, Zev J;
- Puelles, Luis;
- Zeng, Hongkui;
- Rubenstein, John LR;
- Nord, Alex S
Published Web Location
https://doi.org/10.1073/pnas.2108760119Abstract
Enhancers integrate transcription factor signaling pathways that drive cell fate specification in the developing brain. We paired enhancer labeling and single-cell RNA-sequencing (scRNA-seq) to delineate and distinguish specification of neuronal lineages in mouse medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) at embryonic day (E)11.5. We show that scRNA-seq clustering using transcription factors improves resolution of regional and developmental populations, and that enhancer activities identify specific and overlapping GE-derived neuronal populations. First, we mapped the activities of seven evolutionarily conserved brain enhancers at single-cell resolution in vivo, finding that the selected enhancers had diverse activities in specific progenitor and neuronal populations across the GEs. We then applied enhancer-based labeling, scRNA-seq, and analysis of in situ hybridization data to distinguish transcriptionally distinct and spatially defined subtypes of MGE-derived GABAergic and cholinergic projection neurons and interneurons. Our results map developmental origins and specification paths underlying neurogenesis in the embryonic basal ganglia and showcase the power of scRNA-seq combined with enhancer-based labeling to resolve the complex paths of neuronal specification underlying mouse brain development.
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