PMID- 28704293
OWN - NLM
STAT- MEDLINE
DCOM- 20180423
LR  - 20180423
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 28
IP  - 13
DP  - 2017 Sep 6
TI  - Analysis of neural crest cells from Charcot-Marie-Tooth disease patients 
      demonstrates disease-relevant molecular signature.
PG  - 814-821
LID - 10.1097/WNR.0000000000000831 [doi]
AB  - Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The 
      majority of CMT is demyelinating type (demyelinating CMT) caused by Schwann cell 
      involvement. Although a large number of genes responsible for demyelinating CMT 
      have been found, the common molecular target of the pathophysiology caused by 
      these different genes in demyelinating CMT is still unknown. We generated induced 
      pluripotent stem cells (iPSCs) from healthy controls and patients with 
      demyelinating CMT caused by duplication in peripheral myelin protein 22 kDa 
      (PMP22) or point mutations in myelin protein zero (MPZ) or early growth response 
      2 (EGR2). iPSCs were differentiated into neural crest cells, progenitors of 
      Schwann cells, followed by purification using the neural crest cell markers p75 
      and human natural killer-1. To identify a disease-relevant molecular signature at 
      the early stage of demyelinating CMT, we conducted global gene expression 
      analysis of iPSC-derived neural crest cells and found that a glutathione-mediated 
      detoxification pathway was one of the related pathways in demyelinating CMT. mRNA 
      expression of glutathione S-transferase theta 2 (GSTT2), encoding an important 
      enzyme for glutathione-mediated detoxification, and production of reactive oxygen 
      species were increased in demyelinating CMT. Our study suggested that 
      patient-iPSC-derived neural crest cells could be a cellular model for 
      investigating genetically heterogeneous disease CMT and might provide a 
      therapeutic target for the disease.
FAU - Kitani-Morii, Fukiko
AU  - Kitani-Morii F
AD  - aCenter for iPS Cells for Research and Application (CiRA) bInstitute for Frontier 
      Medical Sciences, Kyoto University cDepartment of Neurology dNorth Medical 
      Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
FAU - Imamura, Keiko
AU  - Imamura K
FAU - Kondo, Takayuki
AU  - Kondo T
FAU - Ohara, Ryo
AU  - Ohara R
FAU - Enami, Takako
AU  - Enami T
FAU - Shibukawa, Ran
AU  - Shibukawa R
FAU - Yamamoto, Takuya
AU  - Yamamoto T
FAU - Sekiguchi, Kazuya
AU  - Sekiguchi K
FAU - Toguchida, Junya
AU  - Toguchida J
FAU - Mizuno, Toshiki
AU  - Mizuno T
FAU - Nakagawa, Masanori
AU  - Nakagawa M
FAU - Inoue, Haruhisa
AU  - Inoue H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (EGR2 protein, human)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Myelin P0 Protein)
RN  - 0 (Myelin Proteins)
RN  - 0 (PMP22 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.5.1.- (GSTT2 protein, human)
RN  - EC 2.5.1.18 (Glutathione Transferase)
SB  - IM
MH  - Charcot-Marie-Tooth Disease/genetics/*pathology
MH  - Early Growth Response Protein 2/*genetics
MH  - Female
MH  - Gene Expression
MH  - Glutathione Transferase/*genetics/metabolism
MH  - Humans
MH  - Induced Pluripotent Stem Cells/pathology
MH  - Male
MH  - Myelin P0 Protein/*genetics
MH  - Myelin Proteins/*genetics/metabolism
MH  - Neural Crest/*pathology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2017/07/14 06:00
MHDA- 2018/04/24 06:00
CRDT- 2017/07/14 06:00
PHST- 2017/07/14 06:00 [pubmed]
PHST- 2018/04/24 06:00 [medline]
PHST- 2017/07/14 06:00 [entrez]
AID - 10.1097/WNR.0000000000000831 [doi]
PST - ppublish
SO  - Neuroreport. 2017 Sep 6;28(13):814-821. doi: 10.1097/WNR.0000000000000831.