Modeling Ataxia - Telangiectasia with Induced Pluripotent Stem Cell-Derived Purkinje Cells
Abstract
The purpose and scope of this research is to generate a model system to study human ataxia-telangiectasia patient Purkinje cells and define molecular differences between induced pluripotent stem cell (iPSC)-derived Purkinje cells (PCs) from patients, from unaffected siblings, and from mouse PCs. Major findings include analysis of patient and control iPS lines, differentiation to mature PCs, and initial morphological characterization as well as publication of our studies defining the model system. Patient cells did not display ATM kinase response to DNA damage in either the pluripotent state or the differentiated state, confirming their designation as patient cells. PCs from patient cells were found to have decreased soma size, nuclear size, nuclear circularity, and thinner primary dendrites. Ongoing experiments are examining gene expression and phosphoproteomics. Our model human pluripotent stem cell-derived PC model system, where gene signatures of human embryonic stem cell-derived PCs were compared to mouse PCs, was published in the Proceedings of the National Academy of Sciences.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1135328
Entities
People
- Mary E. Hatten
Organizations
- The Rockefeller University