RESUMO
Human skin fibroblasts were isolated from a 40-year-old hereditary spastic paraplegia patient carrying an intronic splice site mutation (c.1687+2T>A) in SPAST, leading to hereditary spastic paraplegia type 4 (SPG4). Fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated transgene-free line iPS-SPG4-splice retained the specific mutation with no additional genomic aberrations, expressed pluripotency markers and was able to differentiate into cells of all germ layers in vitro. The generated iPS-SPG4-splice line might be a useful platform to study the pathomechanism of SPG4.
Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Paraplegia Espástica Hereditária/patologia , Espastina/genética , Adulto , Diferenciação Celular , Linhagem Celular , Reprogramação Celular , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Fibroblastos/citologia , Heterozigoto , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Microscopia de Fluorescência , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA/genética , Análise de Sequência de DNA , Pele/citologia , Paraplegia Espástica Hereditária/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
An increase in autoimmune diseases poses a socioeconomic challenge worldwide. Predisposing genetic risk has been identified, yet environmental factors make up a significant part of the risk in disease initiation and propagation. Next to improved hygiene and a gross reduction of infections, changes in dietary habits are one of the most evident Western lifestyle factors potentially associated with the increase in autoimmune diseases. Growing evidence suggests that particularly a typical 'Western diet', rich in saturated fat and salt and related pathologies can have a profound impact on local and systemic immune responses under physiologic and autoimmune conditions such as in multiple sclerosis (MS). In this review, we discuss recent findings on environmental factors influencing autoimmunity with an emphasis on the impact of 'Western diet' on immune homeostasis and gut microbiota in MS.
