Integrative multi-omic analysis reveals conserved cell-projection deficits in human Down syndrome brains.
Neuron
; 112(15): 2503-2523.e10, 2024 Aug 07.
Article
en En
| MEDLINE
| ID: mdl-38810652
ABSTRACT
Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how triplication of a small gene subset may impinge on diverse aspects of DS brain physiopathology. Here, we took a multi-omic approach and simultaneously analyzed by RNA-seq and proteomics the expression signatures of two diverse regions of human postmortem DS brains. We found that the overexpression of triplicated genes triggered global expression dysregulation, differentially affecting transcripts, miRNAs, and proteins involved in both known and novel biological candidate pathways. Among the latter, we observed an alteration in RNA splicing, specifically modulating the expression of genes involved in cytoskeleton and axonal dynamics in DS brains. Accordingly, we found an alteration in axonal polarization in neurons from DS human iPSCs and mice. Thus, our study provides an integrated multilayer expression database capable of identifying new potential targets to aid in designing future clinical interventions for DS.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encéfalo
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Síndrome de Down
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia