Browsing by Author "Marques, Vera"
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- Characterization of the role of H2S in neuronal differentiation in Trisomy 21Publication . Marques, Vera; Araújo, Inês; Simão, SóniaDown syndrome (DS) is caused by trisomy of chromosome 21 and is one of the most prevalent aneuploidies compatible with life. The characteristics of DS include congenital heart defects, craniofacial abnormalities, gastrointestinal anomalies, leukemia, seizures, early onset of Alzheimer´s disease, and cognitive impairment among others. Disturbances in the neurological signal processing during critical stages of neurogenesis can affect proliferation, migration, and differentiation of stem cells which may be responsible for the mental impairment of these individuals. These features are important to understanding how DS's brain development is affected. The gene coding for cystathionine-beta-synthase (CBS) is present in chromosome 21 with an extra copy in individuals with DS. CBS is one of the enzymes responsible for the cellular production of hydrogen sulfide (H2S). This is a ubiquitous small gaseous signaling molecule that plays an important role in many physiological processes. However, the contribution of H2S to the abnormal neurodevelopment of DS individuals has not been addressed and is currently under investigation under the Araújo lab. In this study, we aimed to evaluate the contribution of H2S in DS fibroblasts prior to reprogramming these cells into induced pluripotent stem cells (iPSC) to be used in the future as a human cellular model to address the role of H2S in neuronal differentiation in DS. To accomplish this objective, fibroblasts collected from Down Syndrome patients and healthy donors were obtained and H2S production was assessed by time-lapse imaging using a fluorescent probe selective for H2S. The fibroblasts were afterward reprogrammed into iPS cells. The levels of intracellular H2S were higher in the DS cell line when compared to the healthy donor cell line. iPS cells from the DS individuals and the healthy donor fibroblasts were reprogrammed with success and both cell lines expressed the main pluripotency markers Sox2, Nanog, and Oct4 observed by immunocytochemistry and flow cytometry analysis. The data obtained in this work and the iPS lines developed will allow in the future the establishment of an important cellular model to study how H2S affects neurodevelopment in DS.