Cell and Tissue Signatures in Trisomy 21 Human Fetal Hearts

Lay Summary: Worldwide 1.35 million babies are born with heart anomalies each year. Among them, patients with Trisomy 21 present with variety of heart defects. As the name suggests, Trisomy 21 patients have an extra chromosome 21. Interestingly, despite the shared genetic abnormality, only about 50% of Trisomy 21 patients will develop heart defects in their lifetime. The reason for this is unclear. The consequences for patients that do develop cardiac defects can be severe,and affected children need extensive surgery right after birth, or heart transplants. Even with the surgical treatment, most patients with congenital heart defects have a shorter life expectancy, are restricted in their physical activity, are more susceptible to additional complications and experience compromised quality of life overall. One reason for the lack of treatment is that the underlying causes for the malformations remain poorly understood. This is due, in part, to a lack of animal models that recapitulate the human disease and would allow for more in depth studies of the disease mechanism. Here we will take advantage of the newly established biorepository for human fetal tissue at Mount Sinai. We will analyze hearts from healthy and Trisomy 21fetuses. Specifically we will determine any changes in the cell types present in patientscompared to healthy hearts, if the cell types express different genes or gene networks, and if there are structural differences between such as the formation of septal defects. Doing these analyses during development, as opposed to in post mortem samples, has the distinct benefit that the time of analysis is closer to the onset of the disease, and thus may help uncover more targetable mechanisms early. The overall goal of the study is to provide an in depth analysis of healthy and Trisomy hearts and to identify the mechanisms responsible for cardiac malformations during development that can be targeted in future clinical approaches.