CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

Lixia Wang; Fei Yi; Lina Fu; Jiping Yang; Si Wang; Zhaoxia Wang; Keiichiro Suzuki; Liang Sun; Xiuling Xu; Yang Yu; Jie Qiao; Juan Carlos Izpisua Belmonte; Ze Yang; Yun Yuan; Jing Qu; Guang Hui Liu

doi:10.1007/s13238-017-0397-3

CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

Lixia Wang, Fei Yi, Lina Fu, Jiping Yang, Si Wang, Zhaoxia Wang, Keiichiro Suzuki, Liang Sun, Xiuling Xu, Yang Yu, Jie Qiao, Juan Carlos Izpisua Belmonte, Ze Yang, Yun Yuan, Jing Qu, Guang Hui Liu^*

^*Corresponding author for this work

Biological, Environmental Sciences and Engineering

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative 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^+/A272C and FUS^+/G1566A mutations, respectively. We further generated 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.

Original language	English (US)
Pages (from-to)	365-378
Number of pages	14
Journal	Protein and Cell
Volume	8
Issue number	5
DOIs	https://doi.org/10.1007/s13238-017-0397-3
State	Published - May 1 2017

Bibliographical note

Publisher Copyright:
© 2017, The Author(s).

Keywords

ALS
CRISPR/Cas9
gene correction
iPSC disease modeling

ASJC Scopus subject areas

Biotechnology
Biochemistry
Drug Discovery
Cell Biology

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10.1007/s13238-017-0397-3

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title = "CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs",

abstract = "Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative 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+/A272C and FUS+/G1566A mutations, respectively. We further generated 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.",

keywords = "ALS, CRISPR/Cas9, gene correction, iPSC disease modeling",

author = "Lixia Wang and Fei Yi and Lina Fu and Jiping Yang and Si Wang and Zhaoxia Wang and Keiichiro Suzuki and Liang Sun and Xiuling Xu and Yang Yu and Jie Qiao and Belmonte, {Juan Carlos Izpisua} and Ze Yang and Yun Yuan and Jing Qu and Liu, {Guang Hui}",

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doi = "10.1007/s13238-017-0397-3",

language = "English (US)",

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TY - JOUR

T1 - CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

AU - Wang, Lixia

AU - Yi, Fei

AU - Fu, Lina

AU - Yang, Jiping

AU - Wang, Si

AU - Wang, Zhaoxia

AU - Suzuki, Keiichiro

AU - Sun, Liang

AU - Xu, Xiuling

AU - Yu, Yang

AU - Qiao, Jie

AU - Belmonte, Juan Carlos Izpisua

AU - Yang, Ze

AU - Yuan, Yun

AU - Qu, Jing

AU - Liu, Guang Hui

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative 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+/A272C and FUS+/G1566A mutations, respectively. We further generated 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.

AB - Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative 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+/A272C and FUS+/G1566A mutations, respectively. We further generated 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.

KW - ALS

KW - CRISPR/Cas9

KW - gene correction

KW - iPSC disease modeling

UR - http://www.scopus.com/inward/record.url?scp=85017450766&partnerID=8YFLogxK

U2 - 10.1007/s13238-017-0397-3

DO - 10.1007/s13238-017-0397-3

M3 - Article

C2 - 28401346

AN - SCOPUS:85017450766

SN - 1674-800X

VL - 8

SP - 365

EP - 378

JO - Protein and Cell

JF - Protein and Cell

IS - 5

ER -

CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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