RNA-seq analysis of human forebrain organoids irradiated with moderate to high doses of ionizing radiation. RNA-seq analysis of human forebrain organoids irradiated with moderate to high doses of ionizing radiation

Prenatal irradiation can cause neurodevelopmental defects which are characterized by a reduction in brain size (microcephaly). The underlying molecular mechanisms in humans have so far not been studied. Here, we leveraged human forebrain organoids as a model for human embryonic brain development to investigate time- and dose-dependent effects of radiation on organoid growth. For this, organoids of 14 days and 56 days old were irradiated with acute X-ray doses of 0.5 Gy or 2 Gy and compared to controls. Using bulk RNA-seq at different early (6 h and 24 h) and late (14 days) time points after irradiation, we investigated mechanisms of radiation-induced growth defects which resulted from activation of the DNA damage response (cell cycle arrest, DNA repair, apoptosis), premature differentiation and the coordinated repression of primary microcephaly genes.