Amyotrophic lateral sclerosis （ALS） is a complex neu- rodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated wit...Amyotrophic lateral sclerosis （ALS） is a complex neu- rodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells （iPSCs） from fibroblasts of familial ALS patients bearing SOD1＋1A27~c and FUS＋/GISe6A mutations, respectively. We further gener- ated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing （RNA-seq） analysis of motor neurons derived from SOD1＋~A272c and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.展开更多
Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,includ...Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,including plasmid,bacterial artificial chromosome,adeno-associated virus vector,zinc finger nuclease,transcription activator-like effecter nuclease,and helper-dependent adenoviral vector.Gene editing has been successfully employed in different aspects of stem cell research such as gene correction,mutation knock-in,and establishment of reporter cell lines(Raya et al.,2009;Howden et al.,2011;Li et al.,2011;Liu et al.,2011b;Papapetrou et al.,2011;Sebastiano et al.,2011;Soldner et al.,2011;Zou et al.,2011a).These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.展开更多
文摘Amyotrophic lateral sclerosis （ALS） is a complex neu- rodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells （iPSCs） from fibroblasts of familial ALS patients bearing SOD1＋1A27~c and FUS＋/GISe6A mutations, respectively. We further gener- ated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing （RNA-seq） analysis of motor neurons derived from SOD1＋~A272c and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
文摘Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,including plasmid,bacterial artificial chromosome,adeno-associated virus vector,zinc finger nuclease,transcription activator-like effecter nuclease,and helper-dependent adenoviral vector.Gene editing has been successfully employed in different aspects of stem cell research such as gene correction,mutation knock-in,and establishment of reporter cell lines(Raya et al.,2009;Howden et al.,2011;Li et al.,2011;Liu et al.,2011b;Papapetrou et al.,2011;Sebastiano et al.,2011;Soldner et al.,2011;Zou et al.,2011a).These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.
