Project description:We observed that the deletion of Anp32b led to severe defects in ocular development, such as anophthalmia and microphthalmia. Moreover, Anp32b was highly expressed in the lens, and Anp32b−/− embryos with microphthalmia typically exhibited severely impaired lens development. Mechanistically, ANP32B directly interacted with paired box protein 6 (PAX6), a master transcriptional regulator of ocular development, and enhanced its transcriptional activity. In line with these findings, overexpression of PAX6 partially but significantly reversed the inhibition of proliferation observed in ANP32B knockdown cells. Collectively, our findings reveal that ANP32B-deficiency suppresses ocular development by repression of PAX6 and identify ANP32B as a viable therapeutic target for ocular developmental defects.
Project description:This study characterizes the transcriptional dynamics underlying cortical brain organoid development in the absence of the transcription factor PAX6. A PAX6 null allele was engineered by introducing a premature termination codon causing a frameshift mutation (PTC+1). Single-cell RNA sequencing (scRNA-seq) was performed on samples collected at days 7, 8, and 9 following the initiation of differentiation from human induced pluripotent stem cells (hiPSCs), enabling a detailed temporal analysis of gene expression changes.
