한빛사논문
- 조회565
Andrew J. Lee1†, Changyoun Kim2†, Seongwan Park1, Jaegeon Joo1, Baekgyu Choi1, Dongchan Yang1, Kyoungho Jun3, Junghyun Eom1, Seung-Jae Lee4,5, Sun Ju Chung6, Robert A. Rissman7, Jongkyeong Chung3, Eliezer Masliah2*, Inkyung Jung1*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology(KAIST), Daejeon 34141, Republic of Korea.
2Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
3Schoolof Biological Sciencesand In-stitute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea.
4Department of Biomedical Sciences, Department of Medicine, Neuroscience Research Institute, Convergence Research Center for Dementia, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
5Neuramedy Co. Ltd., Seoul 04796, Republic of Korea.
6Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
7Department Neurosciences, Schoolof Medicine,University of California,San Diego,La Jolla, CA 92093,USA.
†Theseauthorscontributedequallyto this work.
*Correspondingauthors: Eliezer Masliah, Inkyung Jung
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder. However, cell type–dependent transcriptional regulatory programs responsible for PD pathogenesis remain elusive. Here, we establish transcriptomic and epigenomic landscapes of the substantia nigra by profiling 113,207 nuclei obtained from healthy controls and patients with PD. Our multiomics data integration provides cell type annotation of 128,724 cis-regulatory elements (cREs) and uncovers cell type–specific dysregulations in cREs with a strong transcriptional influence on genes implicated in PD. The establishment of high-resolution three-dimensional chromatin contact maps identifies 656 target genes of dysregulated cREs and genetic risk loci, uncovering both potential and known PD risk genes. Notably, these candidate genes exhibit modular gene expression patterns with unique molecular signatures in distinct cell types, highlighting altered molecular mechanisms in dopaminergic neurons and glial cells including oligodendrocytes and microglia. Together, our single-cell transcriptome and epigenome reveal cell type–specific disruption in transcriptional regulations related to PD.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-24)
- 국내(교신)+국외 연구진
- 생명과학 > 유전자발현
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