A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion.
Sci Rep
; 13(1): 7689, 2023 05 11.
Article
em En
| MEDLINE
| ID: mdl-37169815
ABSTRACT
22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb "A-D" deletion at this locus. The ~ 1.5 Mb "A-B" deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 "A-B" deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Síndrome de DiGeorge
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos