Author(s) | |
---|---|
Abstract |
Down syndrome is a complex developmental disorder that affects over 400,000 people in the United States and results from the triplication of human chromosome 21. Down syndrome is the most prevalent genetic cause of intellectual disability. While Down syndrome has been modeled in mice, the genes orthologous to human chromosome 21 are spread between mouse chromosomes 10, 16, and 17. This means replicating this disorder in mice has been difficult. Thus, the creation of a human model of this disorder would greatly improve our understanding of Down syndrome. Here, we used direct reprogramming to convert human fibroblasts into induced neurons (iNs). We introduced four transcription factors (Brn2, Ascl1, Myt1l, and NeuroD1 (BAMN)) into human Down syndrome fibroblasts via lentiviral mediated gene transfer. Expression of these factors, in combination with specific media and growth factors, resulted in the reprogramming of human fibroblasts into neuronal cells. As a control, we also reprogrammed fibroblasts from a healthy human subject that was age, sex, and race matched to the individual with Down syndrome. We found that Down syndrome fibroblasts can be converted into induced neurons. We are currently in the process of confirming this process using neuronal-specific markers and karyotyping. This is a novel discovery as it was not previously known if Down syndrome fibroblasts could successfully be converted to neurons using direct reprogramming. Using this new human model, we can gain a better understanding into the mechanisms underlying Down syndrome, as well as gain insight into treatments for this disorder. |
Format | |
Publication Date |
2017-03-21
|
Contributor(s) |
Faculty Mentor
Dr. Kristy Welshhans Dr. Shruti Jain
Ms. Leah Kershner
|
Subject | |
Modified Abstract |
Down syndrome is a complex developmental disorder that results from the triplication of human chromosome 21. Here, we used direct reprogramming to convert human fibroblasts into induced neurons and create a human model of this disorder. We introduced four transcription factors into human Down syndrome fibroblasts and a healthy control via lentiviral mediated gene transfer. We found that Down syndrome fibroblasts can be converted into induced neurons and are in the process of confirming this using neuronal-specific markers. This is a novel discovery, as it was not previously known if Down syndrome fibroblasts could successfully be converted to neurons using direct reprogramming. We will now use this model to gain a better understanding into Down syndrome, as well as insight into treatments for this disorder. |
Comments | |
Permalink | https://oaks.kent.edu/ugresearch/2017/biomedical/1 |
Generating induced neurons from human Down syndrome fibroblasts by direct reprogramming
Bailey, S. (2017). Generating induced neurons from human Down syndrome fibroblasts by direct reprogramming (1–). https://oaks.kent.edu/node/5446
Bailey, Samantha. 2017. “Generating Induced Neurons from Human Down Syndrome Fibroblasts by Direct Reprogramming”. https://oaks.kent.edu/node/5446.
Bailey, Samantha. Generating Induced Neurons from Human Down Syndrome Fibroblasts by Direct Reprogramming. 21 Mar. 2017, https://oaks.kent.edu/node/5446.
My poster and myself