Home > Publications Database > Single-nucleus chromatin accessibility profiling highlights distinct astrocyte signatures in progressive supranuclear palsy and corticobasal degeneration. > print

001     165111
005     20230915090605.0
024 7 _ |a pmc:PMC9468099
|2 pmc
024 7 _ |a 10.1007/s00401-022-02483-8
|2 doi
024 7 _ |a pmid:35976433
|2 pmid
024 7 _ |a 0001-6322
|2 ISSN
024 7 _ |a 1432-0533
|2 ISSN
024 7 _ |a altmetric:134628239
|2 altmetric
037 _ _ |a DZNE-2022-01420
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Briel, Nils
|0 P:(DE-2719)9001545
|b 0
|e First author
|u dzne
245 _ _ |a Single-nucleus chromatin accessibility profiling highlights distinct astrocyte signatures in progressive supranuclear palsy and corticobasal degeneration.
260 _ _ |a Heidelberg
|c 2022
|b Springer
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1674473515_2056
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) exhibit characteristic neuronal and glial inclusions of hyperphosphorylated Tau (pTau). Although the astrocytic pTau phenotype upon neuropathological examination is the most guiding feature in distinguishing both diseases, regulatory mechanisms controlling their transitions into disease-specific states are poorly understood to date. Here, we provide accessible chromatin data of more than 45,000 single nuclei isolated from the frontal cortex of PSP, CBD, and control individuals. We found a strong association of disease-relevant molecular changes with astrocytes and demonstrate that tauopathy-relevant genetic risk variants are tightly linked to astrocytic chromatin accessibility profiles in the brains of PSP and CBD patients. Unlike the established pathogenesis in the secondary tauopathy Alzheimer disease, microglial alterations were relatively sparse. Transcription factor (TF) motif enrichments in pseudotime as well as modeling of the astrocytic TF interplay suggested a common pTau signature for CBD and PSP that is reminiscent of an inflammatory immediate-early response. Nonetheless, machine learning models also predicted discriminatory features, and we observed marked differences in molecular entities related to protein homeostasis between both diseases. Predicted TF involvement was supported by immunofluorescence analyses in postmortem brain tissue for their highly correlated target genes. Collectively, our data expand the current knowledge on risk gene involvement (e.g., MAPT, MAPK8, and NFE2L2) and molecular pathways leading to the phenotypic changes associated with CBD and PSP.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Astrocytes
|2 Other
650 _ 7 |a Corticobasal degeneration
|2 Other
650 _ 7 |a Neurodegeneration
|2 Other
650 _ 7 |a Progressive supranuclear palsy
|2 Other
650 _ 7 |a Tauopathy
|2 Other
650 _ 7 |a snATAC-seq
|2 Other
650 _ 2 |a Astrocytes: pathology
|2 MeSH
650 _ 2 |a Chromatin
|2 MeSH
650 _ 2 |a Corticobasal Degeneration
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: pathology
|2 MeSH
650 _ 2 |a Tauopathies: genetics
|2 MeSH
650 _ 2 |a Tauopathies: pathology
|2 MeSH
650 _ 2 |a tau Proteins: genetics
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
700 1 _ |a Ruf, Viktoria C
|b 1
700 1 _ |a Pratsch, Katrin
|0 P:(DE-2719)2812307
|b 2
|u dzne
700 1 _ |a Roeber, Sigrun
|b 3
700 1 _ |a Widmann, Jeannine
|0 P:(DE-2719)9000813
|b 4
|u dzne
700 1 _ |a Mielke, Janina
|b 5
700 1 _ |a Dorostkar, Mario Manucehr
|0 P:(DE-2719)2812547
|b 6
|u dzne
700 1 _ |a Windl, Otto
|0 P:(DE-2719)2812263
|b 7
|u dzne
700 1 _ |a Arzberger, Thomas
|0 P:(DE-2719)2811333
|b 8
|u dzne
700 1 _ |a Herms, Jochen
|0 P:(DE-2719)2810441
|b 9
|u dzne
700 1 _ |a Strübing, Felix
|0 P:(DE-2719)2813904
|b 10
|e Last author
|u dzne
773 _ _ |a 10.1007/s00401-022-02483-8
|g Vol. 144, no. 4, p. 615 - 635
|0 PERI:(DE-600)1458410-4
|n 4
|p 615 - 635
|t Acta neuropathologica
|v 144
|y 2022
|x 0001-6322
856 4 _ |u https://pub.dzne.de/record/165111/files/DZNE-2022-01420.pdf
|y OpenAccess
856 4 _ |u https://pub.dzne.de/record/165111/files/DZNE-2022-01420.pdf?subformat=pdfa
|x pdfa
|y OpenAccess
909 C O |o oai:pub.dzne.de:165111
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)9001545
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)2812307
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 4
|6 P:(DE-2719)9000813
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 6
|6 P:(DE-2719)2812547
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 7
|6 P:(DE-2719)2812263
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 8
|6 P:(DE-2719)2811333
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 9
|6 P:(DE-2719)2810441
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 10
|6 P:(DE-2719)2813904
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2022
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2021-01-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2021-01-29
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2021-01-29
915 _ _ |a DEAL Springer
|0 StatID:(DE-HGF)3002
|2 StatID
|d 2021-01-29
|w ger
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2022-11-29
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b ACTA NEUROPATHOL : 2021
|d 2022-11-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2022-11-29
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2022-11-29
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b ACTA NEUROPATHOL : 2021
|d 2022-11-29
920 1 _ |0 I:(DE-2719)1110001
|k AG Herms
|l Translational Brain Research
|x 0
920 1 _ |0 I:(DE-2719)1140013
|k Neuropathology / Brainbank
|l Neuropathology / Brainbank
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)1110001
980 _ _ |a I:(DE-2719)1140013
980 _ _ |a UNRESTRICTED
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21