RT Journal Article
SR Electronic
T1 Single Nuclei Sequencing of Human Putamen Oligodendrocytes Reveals Altered Heterogeneity and Disease-Associated Changes in Parkinson’s Disease and Multiple System Atrophy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.06.442967
DO 10.1101/2021.05.06.442967
A1 Teeple, Erin
A1 Joshi, Pooja
A1 Pande, Rahul
A1 Huang, Yinyin
A1 Karambe, Akshat
A1 Latta-Mahieu, Martine
A1 Sardi, S. Pablo
A1 Cedazo-Minguez, Angel
A1 Klinger, Katherine W.
A1 Flores-Morales, Amilcar
A1 Madden, Stephen L.
A1 Rajpal, Deepak
A1 Kumar, Dinesh
YR 2021
UL http://biorxiv.org/content/early/2021/05/07/2021.05.06.442967.abstract
AB The role of oligodendrocytes in neurodegenerative diseases remains incompletely understood and largely unexplored at the single cell level. We profiled 87,086 single nuclei from human brain putamen region for healthy control, Parkinson’s Disease (PD), and Multiple System Atrophy (MSA). Oligodendrocyte lineage cells were the dominant cell-type in the putamen with oligodendrocyte subpopulations clustered by transcriptomic variation found to exhibit diverse functional enrichment patterns, and this oligodendrocyte heterogeneity was altered in a disease-specific way. Among profiled oligodendrocyte subpopulations, differences in expression of SNCA, HAPLN2, MAPT, APP, and OPALIN were observed for PD and MSA compared with healthy controls. Intriguingly, greater activation of unfolded protein response pathway gene expression was observed in PD nuclei versus MSA. Using network analysis, we then identified specific PD- and MSA-correlated gene co-expression modules enriched with disease relevant pathways; the PD-correlated module was significantly enriched for Parkinson’s Disease GWAS loci (p = 0.01046). Our analysis provides a broader understanding of oligodendrocyte heterogeneity and reveals distinctive oligodendrocyte pathological alterations associated with PD and MSA which may suggest potential novel therapeutic targets and new strategies for disease modification.Competing Interest StatementE.T., P.J., R.P., Y.H., A.K., K.W.K., M.L.-M., S.P.S., A.C.-M., S.L.M., D.R., and D.K. are employees of Sanofi and may hold shares and/or stock options in the company.