Epigenomic diversity of cortical projection neurons in the mouse brain
| Autor: | Anna Bartlett, Pengcheng Tan, Hanqing Liu, António Pinto-Duartec, Bertha Dominguez, Minh Vu, Joseph R. Ecker, Yan Pang, Jared B. Smith, Carolyn O’Connor, Megan A. Kirchgessner, Rosa Castanon, Kuo-Fen Lee, M. Margarita Behrens, Elora W Williams, Sheng-Yong Niu, Paula Assakura Miyazaki, Conor Fitzpatrick, Tony Ito-Cole, Lara Boggeman, Edward M. Callaway, Eran A. Mukamel, Joseph R. Nery, Alexis D. Franklin, Mohammad S. Rashid, Matthew W. Jacobs, Cheng-Ta Lee, Andrew Aldridge, Jingtian Zhou, Zhuzhu Zhang, Xin Jin, Angeline Rivkin |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Epigenomics Cell type General Science & Technology 1.1 Normal biological development and functioning Thalamus Population Context (language use) Biology Article Mice Epigenome Underpinning research Neural Pathways medicine Genetics Animals Epigenetics in the nervous system Axon education Projection (set theory) Cerebral Cortex Neurons education.field_of_study Brain Mapping Multidisciplinary Superior colliculus Human Genome Neurosciences Brain Disorders Anterograde tracing medicine.anatomical_structure nervous system Neurological Female Neuroscience |
| Zdroj: | Nature, vol 598, iss 7879 Nature |
| Popis: | Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the 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. Quantitative analysis of the methylation of mouse cortical neurons that project to different cortical and subcortical target regions provides insight into genetic mechanisms that contribute to differences in cell function. |
| Databáze: | OpenAIRE |
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