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Modeling sporadic amyotrophic lateral sclerosis (sALS) has been a challenge since there is no known single gene mutation that triggers disease pathogenesis. Although human induced pluripotent stem cells (hiPSCs) have created new opportunities in studying sALS, they do not retain important age associated phenotypic markers due to the rejuvenation stage

Modeling sporadic amyotrophic lateral sclerosis (sALS) has been a challenge since there is no known single gene mutation that triggers disease pathogenesis. Although human induced pluripotent stem cells (hiPSCs) have created new opportunities in studying sALS, they do not retain important age associated phenotypic markers due to the rejuvenation stage that takes place during the reprogramming of somatic cells into hiPSCs. To overcome this obstacle, we performed an alternative method of direct neuronal conversion from patient fibroblasts that utilizes two transcription factors, Ngn2 and Ascl1. These transcription factors were sufficient to initiate direct neuronal conversion and produce induced neurons (iNeurons). Through the positive staining of neuronal markers Map2, Synapsin-1, and Human Nuclear Marker we found that induced neurons do display neuronal features that are seen in mature neurons.
ContributorsSwinford, Sarah Joan (Author) / Neisewander, Janet (Thesis director) / Sattler, Rita (Committee member) / Nelson, Andrew (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05