skip to main content
Language:
Search Limited to: Search Limited to: Resource type Show Results with: Show Results with: Search type Index

Cell-type-specific gene expression and regulation in the cerebral cortex and kidney of atypical Setbp1 S858R Schinzel Giedion Syndrome mice

Journal of cellular and molecular medicine, 2023-11, Vol.27 (22), p.3565-3577 [Peer Reviewed Journal]

2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. ;ISSN: 1582-1838 ;EISSN: 1582-4934 ;DOI: 10.1111/jcmm.18001 ;PMID: 37872881

Full text available

Citations Cited by
  • Title:
    Cell-type-specific gene expression and regulation in the cerebral cortex and kidney of atypical Setbp1 S858R Schinzel Giedion Syndrome mice
  • Author: Whitlock, Jordan H ; Soelter, Tabea M ; Howton, Timothy C ; Wilk, Elizabeth J ; Oza, Vishal H ; Lasseigne, Brittany N
  • Subjects: Abnormalities, Multiple - genetics ; Abnormalities, Multiple - pathology ; Animals ; Cerebral Cortex - pathology ; Gene Expression ; Humans ; Kidney - pathology ; Mice
  • Is Part Of: Journal of cellular and molecular medicine, 2023-11, Vol.27 (22), p.3565-3577
  • Description: Schinzel Giedion Syndrome (SGS) is an ultra-rare autosomal dominant Mendelian disease presenting with abnormalities spanning multiple organ systems. The most notable phenotypes involve severe developmental delay, progressive brain atrophy, and drug-resistant seizures. SGS is caused by spontaneous variants in SETBP1, which encodes for the epigenetic hub SETBP1 transcription factor (TF). SETBP1 variants causing classical SGS cluster at the degron, disrupting SETBP1 protein degradation and resulting in toxic accumulation, while those located outside cause milder atypical SGS. Due to the multisystem phenotype, we evaluated gene expression and regulatory programs altered in atypical SGS by snRNA-seq of the cerebral cortex and kidney of Setbp1 heterozygous mice (corresponds to the human likely pathogenic SETBP1 variant) compared to matched wild-type mice by constructing cell-type-specific regulatory networks. Setbp1 was differentially expressed in excitatory neurons, but known SETBP1 targets were differentially expressed and regulated in many cell types. Our findings suggest molecular drivers underlying neurodevelopmental phenotypes in classical SGS also drive atypical SGS, persist after birth, and are present in the kidney. Our results indicate SETBP1's role as an epigenetic hub leads to cell-type-specific differences in TF activity, gene targeting, and regulatory rewiring. This research provides a framework for investigating cell-type-specific variant impact on gene expression and regulation.
  • Publisher: England
  • Language: English
  • Identifier: ISSN: 1582-1838
    EISSN: 1582-4934
    DOI: 10.1111/jcmm.18001
    PMID: 37872881
  • Source: Journals@Ovid Open Access Journal Collection Rolling
    MEDLINE
    PubMed Central
    Directory of Open Access Journals
    Wiley Online Library Open Access
    ProQuest Central
Back to results list
INSPIRE LIBRARY - TON DUC THANG UNIVERSITY (84-028) 37 755 057 Feedback
19 Nguyen Huu Tho St. Dist.7, HCM thuvien@tdtu.edu.vn

Copyright © 2017 INSPIRE LIBRARY - TON DUC THANG UNIVERSITY

Searching Remote Databases, Please Wait