Keywords

Neural stem cells; P2Y1 receptor; P2Y2 receptor; Purinergic signaling; Neurogenesis; Cell Proliferation

Abstract

Endogenous neural stem cells (NSCs) are located in specialized niches of the adult brain and play a vital role in both neurogenesis and neuronal repair. However, declines in NSC proliferation and metabolism associated with age and pathology make these cells less efficient at responding to neurodegenerative disease. Understanding signaling pathways that regulate NSC function is therefore essential for the understanding and development of treatments for these conditions. P2Y receptors are G-protein-coupled purinergic receptors that are activated by extracellular nucleotides and regulate cellular metabolism and proliferation. Among the eight known P2Y subtypes, P2Y1 and P2Y2 have been linked to neuronal signaling and Alzheimer’s disease pathology, respectively, suggesting a role in neurodegeneration. This project utilizes human NSCs to assess the effects of P2Y receptor knockdown on NSC proliferation and metabolism. Gene expression analysis confirmed higher baseline P2Y1 and P2Y2 expression in naïve NSCs compared to naïve mesenchymal stem cells, supporting the study of these receptors. Following successful shRNA-mediated lentiviral knockdown of both individual receptors confirmed through gene expression analysis and visible fluorophore expression, cell viability and proliferation were measured. Assay results indicated no significant changes in NSC function and growth following individual receptor knockdown, potentially suggesting a compensatory effect of receptor use in NSC cellular pathways. Interestingly, preliminary findings have indicated an increase in proliferation when both receptors were suppressed simultaneously, although knockdown efficiency was not assessed in these co-knockdown cells. Future studies will further explore the effect of confirmed P2Y1 and P2Y2 co-knockdown on NSC proliferation to expand the understanding of purinergic signaling in these valuable cells.

Thesis Completion Year

2026

Thesis Completion Semester

Spring

Thesis Chair

Sugaya, Kiminobu

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

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Rights Statement

In Copyright