2026-09-20T09:22:41Zhttps://dspace.mit.edu/server/oai/request

oai:dspace.mit.edu:1721.1/1590872025-10-04T03:16:39Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023

Yu, Timothy Lee, Eunjung Alice Kellis, Manolis Edwards, Lilly Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science 2025-04-14T14:04:38Z 2025-04-14T14:04:38Z 2025-02 2025-04-03T14:06:13.854Z https://hdl.handle.net/1721.1/159087 0009-0002-7462-6009 9p deletion (9p-) syndrome is primarily characterized by intellectual disability, developmental delays, and autism. This project investigated how much of the neuronal phenotypes of 9p- syndrome could be attributed to RFX3, a transcription factor and autism risk gene. Bulk RNA-seq data of iPSC-derived neurons from patients with 9p- syndrome and CRISPRengineered cell lines was analyzed using Principal Component Analysis, Differential Gene Expression analysis, and Functional Enrichment analysis. The findings indicate that RFX3 plays a significant role but is not the sole driver of the neuronal phenotypes. SMARCA2, a gene linked to intellectual disability and part of the SWI/SNF complex, was identified as a direct target of RFX3 in the commonly deleted region of chromosome 9p. Notably, the combined deletion of RFX3 and SMARCA2 led to greater dysregulation of SMARCA2 expression and SWI/SNF complex components than the deletion of either gene alone. These findings highlight the potential synergistic effects of RFX3 and SMARCA2 in 9p- syndrome and suggest their combined disruption may underlie the neuronal phenotypes observed. M.Eng. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ Identifying the Role of Transcription Factor RFX3 in 9PDeletion Syndrome Thesis application/pdf Master Master of Engineering in Computer Science and Molecular Biology Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="58cae784-9a6f-4a12-99e0-091ca529d30b"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Identifying the Role of Transcription Factor RFX3 in 9PDeletion Syndrome</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2025-02</PublicationDate> <Authors> <Author> <DisplayName>Edwards, Lilly</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>https://rightsstatements.org/page/InC-EDU/1.0/</License> <Abstract>9p deletion (9p-) syndrome is primarily characterized by intellectual disability, developmental delays, and autism. This project investigated how much of the neuronal phenotypes of 9p- syndrome could be attributed to RFX3, a transcription factor and autism risk gene. Bulk RNA-seq data of iPSC-derived neurons from patients with 9p- syndrome and CRISPRengineered cell lines was analyzed using Principal Component Analysis, Differential Gene Expression analysis, and Functional Enrichment analysis. The findings indicate that RFX3 plays a significant role but is not the sole driver of the neuronal phenotypes. SMARCA2, a gene linked to intellectual disability and part of the SWI/SNF complex, was identified as a direct target of RFX3 in the commonly deleted region of chromosome 9p. Notably, the combined deletion of RFX3 and SMARCA2 led to greater dysregulation of SMARCA2 expression and SWI/SNF complex components than the deletion of either gene alone. These findings highlight the potential synergistic effects of RFX3 and SMARCA2 in 9p- syndrome and suggest their combined disruption may underlie the neuronal phenotypes observed.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>