Analysis of the interaction of genetic background with DYRK1a inhibition on the proliferation and differentiation of mouse embryonic stem cell-derived Neural Precursor Cell

Nicole Da Costa

Document Type

Article

Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory

Abstract

Dual specificity protein kinase DYRK1a is integral to central nervous system development, and has been identified as a Down syndrome candidate gene. The purpose of this experiment was to investigate the role of the interaction between genetic background and DYRK1a inhibition in modifying neural progenitor cells (NPCs) proliferation. We hypothesized that neural cell proliferation and differentiation would be affected by DYRK1a inhibition, and that cell proliferation would be less affected in the WSB cell line than the B6 cell line. DYRK1a was inhibited in mouse embryonic stem cell (mESC) derived NPCs in B6, 129, and WSB cell lines, and NPCs were developed into neurospheres to measure their mean areas while NPCs were also grown adherent to cell plates and cell counts were tracked. After Passage 5 for NPCs grown into neurospheres and Passage 3 for NPCs grown adherent, their differentiation potential was also analyzed using immunofluorescent staining to observe the effects of DYRK1a inhibition on the NPC’s differentiation potential into neurons. Experimental results supported a model in which DYRK1a inhibition by ID-8 has an effect on neural precursor cell proliferation, and where genetically diverse mouse strains have different responses to DYRK1a inhibition.

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