Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain
Blue B. Lake1†, Song Chen1†, Brandon Sos1,4†, Jean Fan2†, Yun Yung3, Gwendolyn E. Kaeser3,4, Thu E. Duong1,5, Derek Gao1, Jerold Chun3*, Peter Kharchenko2*, Kun Zhang1*
1Department of Bioengineering, University of California San Diego, La Jolla, CA, USA; 2Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA; 3Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; 4Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA; 5Department of Pediatric Respiratory Medicine, University of California San Diego, La Jolla, CA, USA
†Equally contributed authors
Detailed characterizations of the cell types comprising the immensely complex human brain is essential to understanding its functionalities. Such tasks require highly scalable experimental approaches to examine different aspects of the molecular state of individual cells, as well as their computational integration to produce unified cell state annotations. Here we outline the development of two highly scalable methods (snDrop-Seq and scTHS-Seq), that we have used to acquire nuclear transcriptome and DNA accessibility maps in thousands of single cells from the human adult primary visual cortex. This has enabled fine resolution of human neuronal subtypes, a majority of the non-neuronal cell types, as well as the cell-type specific nuclear transcriptome and DNA accessibility maps. Integrative analysis has allowed us to identify transcription factors and regulatory elements shaping the state of different brain cell types, and to map genetic risk factors of human brain common diseases to specific pathogenic cell types and subtypes.
Credits: None available.
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