ATOH1 (Atonal BHLH Transcription Factor 1)

Bexarotene activates the Wnt signaling pathway, and treatment with the Wnt inhibitor IWR-1 can partially rescue the neurodevelopmental impairments in embryos. In summary, bexarotene offers new insights into the potential neurodevelopmental risks in zebrafish embryos, emphasizing the importance of preventing drug side effects and ensuring the safe and rational use of medications to protect the health of living organisms.

However, we identify region-specific intracellular pH differences that suggest potential functional heterogeneity. Altogether, this study presents a comprehensive description of best4 + cell development from birth to spatial regulation that will be instrumental to understand how best4 + cells change in disease or might be therapeutically manipulated and presents the tools to dissect their function in vivo .

This suggests that similar differentiation processes may contribute to tumor heterogeneity in patients. This study presents the model system enabling reversible switching between a transformed and differentiated cell state in a human cancer using small-molecule treatment.

To therapeutically target the CR factors, we used histone deacetylase (HDAC) inhibitors to collapse the chromatin architecture and induce topological blurring of superenhancer loops, abrogating core TF expression and halting tumor growth. To our knowledge, our study presents the first example of oncogenic cross-regulation between viral and human epigenomic circuitry to generate interlocking and essential transcriptional feedback circuits that explain why MCPyV causes neuroendocrine cancer and represent a tumor dependency that can be targeted therapeutically.

Close to one-quarter of the DMRs overlap known copy number aberrations in medulloblastoma, nominating potential enhancer and promoter elements impacted by these genomic aberrations. Collectively, our data provide a rich resource to start decoding the functional impact of non-coding variation on gene regulation in the developing cerebellum and on genomic dysregulation in diseases of cerebellar growth.

We also identify NeuroD1 as a co-repressor that collaborates with Sin3A/Hdac1 to inhibit Atoh1 transcription. Our findings highlight the central role of the Sin3A complex in orchestrating distinct stages of cerebellar GC lineage development and may provide insights into Sin3A-related cerebellar disorders and medulloblastoma in human.

Additionally, a 5-lncRNA signature linked to phototransduction was exclusive to Gr3, offering insights into its lineage switch and molecular regulation. Lnc-SMARCA2 and, MGC32805 and LOC107986446, are exclusively deregulated in SHH and Gr4 MB, respectively, and directly associated with group-specific MB oncogenes, representing promising novel biomarkers and therapeutic targets in MB.

Our findings also demonstrated that the FDA-approved madecassic acid effectively mitigates vHC loss resulting from Gpx4 ablation and cisplatin administration through the modulation of Acsl3 and Gpx4. In summary, inhibiting ferroptosis may represent a potential strategy to protect against vestibular dysfunction caused by cisplatin-induced vestibulotoxicity.

Finally, behavioral analysis revealed a hyperlocomotor phenotype in ezh2-/- larvae, consistent with cerebellar dysfunction. Together, these findings identify ezh2 as a key regulator of progenitor maintenance and neuronal differentiation in the cerebellum, highlighting its crucial role in establishing functional cerebellar circuits.

We showed that NMs from ybx1 mutant zebrafish larvae display consistent, regeneration-specific deficits in HC number and initiate both HC regeneration and atoh1a expression 20% slower than in wild-type siblings. By demonstrating that ybx1 promotes rapid HC regeneration through early atoh1a upregulation, the results support DELAY's ability to identify key temporal regulators of gene expression.

Transcriptomics of 944 human SCLCs revealed a basal-like subset and a tuft-ionocyte-like state that altogether demonstrate notable conservation between cancer states and normal basal cell injury response mechanisms10-13. Together, these data indicate that the basal cell is a probable origin for SCLC and other neuroendocrine-tuft cancers that can explain neuroendocrine-tuft heterogeneity, offering new insights for targeting lineage plasticity.

This review offers a comprehensive overview of the current understanding of the genetic and epigenetic pathways crucial for Merkel cell differentiation. It covers the implication of Merkel cell-specific developmental programs, the role of epigenetic regulatory Polycomb complexes, and how genetic and epigenetic mechanisms converge to orchestrate Merkel cell differentiation.