| First Author | Ressler AK | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 1 | Pages | 105797 |
| PubMed ID | 36594023 | Mgi Jnum | J:334380 |
| Mgi Id | MGI:7424380 | Doi | 10.1016/j.isci.2022.105797 |
| Citation | Ressler AK, et al. (2023) Evidence of shared transcriptomic dysregulation of HNRNPU-related disorder between human organoids and embryonic mice. iScience 26(1):105797 |
| abstractText | Generating effective therapies for neurodevelopmental disorders has remained elusive. An emerging drug discovery approach for neurodevelopmental disorders is to characterize transcriptome-wide dysregulation in an appropriate model system and screen therapeutics based on their capacity to restore functionally relevant expression patterns. We characterized transcriptomic dysregulation in a human model of HNRNPU-related disorder to explore the potential of such a paradigm. We identified widespread dysregulation in functionally relevant pathways and then compared dysregulation in a human model to transcriptomic differences in embryonic and perinatal mice to determine whether dysregulation in an in vitro human model is partially replicated in an in vivo model of HNRNPU-related disorder. Strikingly, we find enrichment of co-dysregulation between 45-day-old human organoids and embryonic, but not perinatal, mice from distinct models of HNRNPU-related disorder. Thus, hnRNPU deficient human organoids may only be suitable to model transcriptional dysregulation in certain cell types within a specific developmental time window. |
