DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects.

ABSTRACT: The 22q11.2 deletion syndrome (22qDS) is a human disorder where the majority of clinical manifestations originate during embryonic development. 22qDS is caused by a microdeletion in one chromosome 22, including DGCR8, an essential gene for microRNA (miRNA) production. However, the impact of DGCR8 hemizygosity on human development is still unclear. In this study, we generated two human pluripotent cell models containing a single functional DGCR8 allele to elucidate its role in early development. DGCR8+/- human embryonic stem cells (hESCs) showed increased apoptosis as well as self-renewal and differentiation defects in both the naïve and primed states. The expression of primate-specific miRNAs was largely affected, due to impaired miRNA processing and chromatin accessibility. DGCR8+/- hESCs

SUBMITTER: Colomer-Boronat A 

PROVIDER: S-EPMC11941479 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature