Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy

Yuhao Min, Xue Wang, Özkan İş, Tulsi A. Patel, Junli Gao, Joseph S. Reddy, Zachary S. Quicksall, Thuy Nguyen, Shu Lin, Frederick Q. Tutor-New, Jessica L. Chalk, Adriana O. Mitchell, Julia E. Crook, Peter T. Nelson, Linda J. Van Eldik, Todd E. Golde, Minerva M. Carrasquillo, Dennis W. Dickson, Ke Zhang, Mariet Allen and Nilüfer Ertekin-Taner ()
Additional contact information
Yuhao Min: Mayo Clinic
Xue Wang: Mayo Clinic
Özkan İş: Mayo Clinic
Tulsi A. Patel: Mayo Clinic
Junli Gao: Mayo Clinic
Joseph S. Reddy: Mayo Clinic
Zachary S. Quicksall: Mayo Clinic
Thuy Nguyen: Mayo Clinic
Shu Lin: Mayo Clinic
Frederick Q. Tutor-New: Mayo Clinic
Jessica L. Chalk: Mayo Clinic
Adriana O. Mitchell: Mayo Clinic
Julia E. Crook: Mayo Clinic
Peter T. Nelson: University of Kentucky
Linda J. Van Eldik: University of Kentucky
Todd E. Golde: Emory University
Minerva M. Carrasquillo: Mayo Clinic
Dennis W. Dickson: Mayo Clinic
Ke Zhang: Mayo Clinic
Mariet Allen: Mayo Clinic
Nilüfer Ertekin-Taner: Mayo Clinic

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by cell-type-specific tau lesions in neurons and glia. Prior work uncovered transcriptome changes in human PSP brains, although their cell-specificity is unknown. Further, systematic data integration and experimental validation platforms to prioritize brain transcriptional perturbations as therapeutic targets in PSP are currently lacking. In this study, we combine bulk tissue (n = 408) and single nucleus RNAseq (n = 34) data from PSP and control brains with transcriptome data from a mouse tauopathy and experimental validations in Drosophila tau models for systematic discovery of high-confidence expression changes in PSP with therapeutic potential. We discover, replicate, and annotate thousands of differentially expressed genes in PSP, many of which reside in glia-enriched co-expression modules and cells. We prioritize DDR2, STOM, and KANK2 as promising therapeutic targets in PSP with striking cross-species validations. We share our findings and data via our interactive application tool PSP RNAseq Atlas ( https://rtools.mayo.edu/PSP_RNAseq_Atlas/ ). Our findings reveal robust glial transcriptome changes in PSP, provide a cross-species systems biology approach, and a tool for therapeutic target discoveries in PSP with potential application in other neurodegenerative diseases.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42626-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42626-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42626-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().