Based on the observation that treatment with atRA did not maintain long-term over-expression of SOX9 (Supplementary Fig. 5c), we postulated that the epigenetic rewiring of the 3D enhancer network could support the adaptation of MD tumoroids to recurrent RA stimuli, driving an enhanced transcriptional bursting through the establishment of transcriptional memory (Fig. 5b)16,18,19,49,50. Here, SOX9 is linked to Menkes disease.