Epigenomic Diversity of Cortical Projection Neurons in the Mouse Brain
| Autor: | Cheng-Ta Lee, Joseph R. Nery, Tony Ito, Angeline Rivkin, Joseph R. Ecker, Lara Boggeman, Pengcheng Tan, Zhuzhu Zhang, Minh Vu, Jared B. Smith, Xin Jin, Kuo-Fen Lee, Paula Assakura Miyazaki, Jingtian Zhou, Matthew W. Jacobs, Anna Bartlett, Eran A. Mukamel, Bertha Dominguez, Alexis D. Franklin, Megan A. Kirchgessner, Hanqing Liu, Yan Pang, Conor Fitzpatrick, Andrew Aldridge, Elora W Williams, Edward M. Callaway, Carolyn O’Connor, Mohammad S. Rashid, Sheng-Yong Niu, Rosa Castanon, M. Margarita Behrens |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Cell type education.field_of_study Superior colliculus Thalamus Population Context (language use) Biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure nervous system medicine Axon Projection (set theory) education Neuroscience 030217 neurology & neurosurgery 030304 developmental biology Epigenomics |
| DOI: | 10.1101/2020.04.01.019612 |
| Popis: | SummaryNeuronal cell types are classically defined by their molecular properties, anatomy, and functions. While recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain, neuronal cell types are often studied out of the context of their anatomical properties. To better understand the relationship between molecular and anatomical features defining cortical neurons, we combined retrograde labeling with single-nucleus DNA methylation sequencing to link epigenomic properties of cell types to neuronal projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical (CC) and cortico-subcortical long-distance projections. Our results revealed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. Based on their epigenomes, intra-telencephalic (IT) cells projecting to different cortical targets could be further distinguished, and some layer 5 neurons projecting to extra-telencephalic targets (L5-ET) formed separate subclusters that aligned with their axonal projections. Such separation varied between cortical areas, suggesting area-specific differences in L5-ET subtypes, which were further validated by anatomical studies. Interestingly, a population of CC projection neurons clustered with L5-ET rather than IT neurons, suggesting a population of L5-ET cortical neurons projecting to both targets (L5-ET+CC). We verified the existence of these neurons by labeling the axon terminals of CC projection neurons and observed clear labeling in ET targets including thalamus, superior colliculus, and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties. |
| Databáze: | OpenAIRE |
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