Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A41]

Investigating Tau Isoform Expression in Chimp iPSC-Derived Astrocytes

Presenter: Karishma Mahesh Babani

Faculty Sponsor: Courtney Babbitt

School: UMass Amherst

Research Area: Biology

ABSTRACT

Humans and chimpanzees share approximately 98% of their DNA sequence, making chimps an invaluable resource for studying human health and disease. Tauopathies are characterized by abnormal accumulation of the tau protein, which is encoded by the Microtubule-Associated Protein Tau(MAPT) gene. Humans have six tau isoforms encoded by the MAPT gene, with 3 or 4 repeat regions (3R or 4R) resulting from alternative splicing. Exons 9 and 10 encode portions of this repeat region. While exon 9 is constitutively included, exon 10 inclusion produces the fourth repeat, generating 4R tau. Exon 10 splicing instability is strongly associated with tau aggregation and neurodegeneration. We use comparative differences to examine the protein tau and its role in tauopathies. Human neurodegenerative diseases (e.g., Alzheimer's, a tauopathy) occur more frequently than in non-human primates. Human iPSC-derived astrocytes mostly express 3R tau; however, it is unclear if chimpanzee iPSC-derived astrocytes express 4R tau and how their splicing patterns differ. Variations in exon 10 inclusion among species may affect susceptibility to tau disease, since astrocytes assist in tau propagation. We used wet-lab methods and bioinformatics to determine whether chimpanzee astrocytes express 4R tau transcripts using isoform-specific PCR primers targeting splicing sites, including exon 10. Studies on MAPT splicing, tau fragments like K18, and mutations like P301S demonstrate the connection between tau aggregation and illness and various tau isoforms, especially 4R. Examining splicing patterns in exons 9 and 10 aims to clarify lineage-specific regulation of MAPT and to assess how chimpanzees can help humans understand the roots of neurodegenerative disease.

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