Identifying the Role of Transcription Factor RFX3 in 9PDeletion Syndrome

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.

Name thesis:degree_name

Master

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2025

Author dc:creator

• Edwards, Lilly

Advisors dc:contributor.advisor

• Yu, Timothy
• Lee, Eunjung Alice
• Kellis, Manolis

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright retained by author(s)

Licence dc:rights.uri

• https://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/159087

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/159087