| Experiment Id | GSE150010 | Name | Enhancer decommissioning during inner ear maturation imposes an epigenetic barrier to sensory hair cell regeneration |
| Experiment Type | RNA-Seq | Study Type | Baseline |
| Source | GEO | Curation Date | 2023-07-21 |
| description | Latent transdifferentiation potential exists in supporting cells at neonatal stage in the organ of Corti in mouse, but this plasticity is lost rapidly during the first week of postnatal maturation, leading to the failure of sensory hair cell regeneration. To investigate the molecular mechanism underlying the loss of transdifferentiation potential, we compared epigenetic changes in E17.5, P1 and P6 supporting cells. In E17.5 and P1 supporting cells, hair cell gene enhancers are kept in a primed state (H3K4me1+ H3K27ac-) which can be readily activated during transdifferentiation induced by Notch blocking. As supporting cells mature, a substantial amount of hair cell gene enhancers are decommissioned by H3K4me1, leading to the loss of transdifferentiation potential. In contrast, hair cell gene enhancers retain their commissioned epigenetic status in mature utricular supporting cells, sustaining the transidifferentiation potential in utricular supporting cells in mature animals. Our findings reveal the epigenetic mechanisms underlying the failure of sensory hair cell regeneration in mammalian cochlea. P1 cochlear sensory hair cells (Atoh1-GFP+) were FACS purified for transcriptome and epigenetic profiling to hair cell gene identification and enhancer prediction. E17.5, P1 and P6 supporting cells (Lfng-GFP+) were collected for transcriptomic and epigenetic analyses to survey the epigenetic changes surrounding hair cell gene elements. Activation of hair cell gene elements was interrogated by comparing epigenetic profiles between transdifferentiating supporting cells (permissive; Lfng-CreER/TdTomato+ Atoh1-GFP+) and non-transdifferentiating supporting cells (non-permissive; Lfng-CreER/TdTomato+). In addition, P21 utricular supporting cells (Lfng-GFP+) were compared to their cochlear counterpart. |
