Center for Epigenomics of the Mouse Brain Atlas
Molecular Neurobiology Lab, Xin Jin
Salk Institute for Biological Studies
University of California San Diego
San Diego, CA
I am part of a nation-wide collaboration guided by the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and more specifically the sub-category, NIH Brain Initiative Cell Census Network (BICCN). Our research team aims to advance the understanding between the epigenetic properties of cell types to their anatomical features and neuronal connectivity by utilizing retrograde tracing with single nucleus DNA methylation sequencing. I am responsible for conducting the essential AAVretro-cre virus injection that labels a targeted brain region in conjunction with the afferent projections from other areas. With my successful targeting and their detailed analysis, together we have determined how individual neurons have unique epigenetic signatures that dictate laminar location, region, and projection target. Moreover, this data has been essential for analyzing the molecular landscape of the motor cortex across species. Through diligent teamwork and considerable amounts of communication, two manuscripts are currently under review at Nature. Importantly, understanding these components will enable scientists to further study and manipulate these projection neurons of interest within the context of their anatomical properties.
Figure. Neural characteristics explored through Epi-Retro-Seq. (A) The retrograde tracer (AAV2 retro-cre) was injected into one of the cortical or extra-telencephalic targets in INTACT knock-in mice. (B) The nuclei of neurons projecting to injected targets were labeled and were dissected to isolate nuclei through fluorescence activated nuclei sorting (FANS) then snmC-seq2 sequencing. (C) Example of distribution of cell clusters projected to ventral tegmental area. (D) Same workflow as previously described with emphasis on the primary motor cortex
Epigenomic Diversity of Cortical Projection Neurons in the Mouse Brain
Zhuzhu Zhang, Jingtian Zhou1, Pengcheng Tan1 Yan Pang, Angeline Rivkin1, Megan, Kirchgessner, Elora Williams, Cheng-Ta Lee, Hanqing Liu1, Alexis D. Franklin, Paula Assakura, Miyazaki, Anna Bartlett, Andrew Aldridge, Minh Vu, Lara Boggeman, Conor Fitzpatrick, Joseph R. Nery1, Rosa G. Castanon, Mohammad Rashid, Matthew Jacobs, Tony Ito, Bertha Dominguez, Sheng Yong Niu1, Jared B. Smith, Caz O'Connor, Kuo-Fen Lee, Xin Jin, Eran A. Mukamel, M. Margarita Behrens, Joseph R. Ecker, and Edward M. Callaway
A multimodal cell census and atlas of the mammalian primary motor cortex