Human pluripotent stem cells (PSCs), particularly human induced PSCs (iPSCs) from patients, offer a novel model system to reveal cellular and molecular events underlying normal and abnormal development, as well as a means to better understand human disease pathogenesis. Studies using iPSCs are especially valuable for enhancing our understanding of complex traits associated with Down syndrome (DS) that cannot be fully recapitulated in animal models. Yet, despite their incredible utility, human PSC studies encounter issues that significantly impede research progress in the field. Variability in iPSCs hinders the progress to identify robust phenotypes and limits utility for drug screening. To address this challenge for Down syndrome, mosaicism (the presence of cells that are derived from a single zygote and are genetically identical except for the presence [or absence] of an additional chromosome 21) can be exploited to generate isogenic cells.
We aim to work with individuals who have mosaic DS to create isogenic trisomy 21 and euploid iPSCs to validate disease related phenotypes.

Public Health Relevance

As the most common genetic cause of intellectual disability, Down syndrome is a public health concern. The proposed research will create new models of Down syndrome to advance the study of Down syndrome neuropathophysiology. The aims of this proposal include generating Down syndrome-specific human pluripotent stem cells from non-embryonic sources.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD092640-01A1
Application #
9527495
Study Section
National Institute of Child Health and Human Development Initial Review Group (CHHD)
Program Officer
Parisi, Melissa
Project Start
2018-04-01
Project End
2020-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Pediatrics
Type
Graduate Schools
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715