Biomaterial Database

Epigenomic diversity of cortical projection neurons in the mouse brain. 2021

Zhuzhu Zhang, and Jingtian Zhou, and Pengcheng Tan, and Yan Pang, and Angeline C Rivkin, and Megan A Kirchgessner, and Elora Williams, and Cheng-Ta Lee, and Hanqing Liu, and Alexis D Franklin, and Paula Assakura Miyazaki, and Anna Bartlett, and Andrew I Aldridge, and Minh Vu, and Lara Boggeman, and Conor Fitzpatrick, and Joseph R Nery, and Rosa G Castanon, and Mohammad Rashid, and Matthew W Jacobs, and Tony Ito-Cole, and Carolyn O'Connor, and António Pinto-Duartec, and Bertha Dominguez, and Jared B Smith, and Sheng-Yong Niu, and Kuo-Fen Lee, and Xin Jin, and Eran A Mukamel, and M Margarita Behrens, and Joseph R Ecker, and Edward M Callaway

Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009434	Neural Pathways	Neural tracts connecting one part of the nervous system with another.	Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001931	Brain Mapping	Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures.	Brain Electrical Activity Mapping,Functional Cerebral Localization,Topographic Brain Mapping,Brain Mapping, Topographic,Functional Cerebral Localizations,Mapping, Brain,Mapping, Topographic Brain
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005260	Female		Females
D000081122	Epigenome	A network of chemical compounds surrounding DNA that modify the genome without altering the DNA sequences and have a role in determining which genes are active in a cell.	DNA Methylome,Methylome,DNA Methylomes,Epigenomes,Methylome, DNA,Methylomes,Methylomes, DNA
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057890	Epigenomics	The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.	Epigenetics,Epigenetic,Epigenomic