NIH Grant to Support Breakthrough Stem Cell Models for Down Syndrome at UW The Badger Herald
Anita Bhattacharyya, professor of cell and regenerative biology at the University of Wisconsin, leads innovative research to understand how changes in brain development in the womb lead to intellectual disability in people with Down syndrome at the UW Waisman Center .
This approach aims to shed light on how brain development in people with Down syndrome differs from that in typically developing people and to find potential targets for therapy.
Down syndrome is a genetic disease that occurs when abnormal cell division results in the addition of an extra chromosome to chromosome 21, also known as trisomy 21. Although the genetic cause of Down syndrome and its effects phenotypic associated are well studied, there are gaps in the understanding of how prenatal brain development with Down syndrome differs from those without the disorder.
The researchers received an $ 11 million transformative research grant from the National Institutes of Health, also known as NIH. This grant is awarded to research that the NIH considers to be highly innovative and likely to have a significant impact in the biomedical and behavioral fields.
The primary method of studying the disease currently uses animal models that do not accurately represent how the disease presents itself in humans. Bhattacharyya and colleagues are developing a new technique for modeling the prenatal brain of Down syndrome based on human-induced pluripotent stem cells, also known as iPSC.
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According to NIHSince scientists are unable to manipulate human development as they can with animal model organisms for ethical reasons, much of the developmental information has been extrapolated from experiments and studies on model organisms. Although these models were essentiall in development studies, the iPSC offer a new way to study embryonic development using human cells instead of model organisms.
Human-induced pluripotent cells start either as adult skin or as blood cells which can then be reprogrammed to become almost any other type of cell. Bhattacharyya and his colleagues use iPSCs from adults with Down syndrome and reprogram them into neural cells – cells located in the brain, particularly the prefrontal cortex – to study how neural development pathways in Down syndrome diverge from the brain. neurotypical pathway.
“Although Down syndrome is quite common and we know a lot about people with Down syndrome… what we don’t fully understand is how brain development in Down syndrome is different.” , said Bhattacharyya.
Bhattacharyya, Su-Chun Zhang, UW School of Medicine and Public Health Professors of Neuroscience and Neurology and other collaborators from Waisman and the University of Washington-Seattle and Seattle Children’s Hospital, hope to compare reprogrammed stem cells to prenatal tissue to confirm that iPSC is a viable model to study the prenatal development of Down syndrome. If this is confirmed, prenatal tissue, to which researchers have limited access, may no longer be needed to study prenatal development.
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Waisman Center investigator Daifeng Wang, professor of biostatistics, medical informatics and informatics, and André Sousa, professor of neuroscience, will collaborate on the project. Bhattacharyya said Sousa’s expertise in unique cell sequencing in human brain development and Wang’s valuable computer skills are incredibly relevant to this project.
Zhang’s lab is also studying the differences between the functions of neurons in people with Down’s syndrome. Previous findings by Bhattacharyya and Zhang have led them to believe that the neurons of people with Down syndrome are not as active as those of people without. This new research model will hopefully allow researchers to delve into the reason for this phenomenon.
Dr Sigan Hartley, assistant professor of human development and family studies at UW, also studies Down syndrome among other developmental disorders. She said Bhattacharyya’s line of research is very exciting for the Down syndrome community.
“Bhattacharyya’s work can significantly advance our understanding of cognitive and health impairments seen in people with Down syndrome, which have a dramatic impact on their quality of life,” Hartley said. “These conditions include things like intellectual disability, Alzheimer’s disease, leukemia, and congenital heart disease.”
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The objective of this project is to build an atlas of the prefrontal cortex in trisomy 21. They will map the specific molecular pathways and types of neurons that differ in Down syndrome, with a particular focus on prenatal development and the right period. after birth.
Bhattacharrya said the atlas will give them a roadmap on what happens in prenatal brain development in Down syndrome. Using this atlas, researchers can determine whether iPSC-derived cells mimic differences in prenatal brain development in people with Down syndrome.
“This is my dream project, and it took 15 years to achieve it because several things had to happen,” said Bhattacharyya. “First, we had to bring together the right people to do this kind of project. “