PMID- 30581017
OWN - NLM
STAT- MEDLINE
DCOM- 20200227
LR  - 20200309
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 12
IP  - 1
DP  - 2019 Jan 8
TI  - Neuron-Glia Interactions Increase Neuronal Phenotypes in Tuberous Sclerosis 
      Complex Patient iPSC-Derived Models.
PG  - 42-56
LID - S2213-6711(18)30488-0 [pii]
LID - 10.1016/j.stemcr.2018.11.019 [doi]
AB  - Tuberous sclerosis complex (TSC) is a rare neurodevelopmental disorder resulting 
      from autosomal dominant mutations in the TSC1 or TSC2 genes, leading to a 
      hyperactivated mammalian target of rapamycin (mTOR) pathway, and gray and white 
      matter defects in the brain. To study the involvement of neuron-glia interactions 
      in TSC phenotypes, we generated TSC patient induced pluripotent stem cell 
      (iPSC)-derived cortical neuronal and oligodendrocyte (OL) cultures. TSC neuron 
      mono-cultures showed increased network activity, as measured by calcium 
      transients and action potential firing, and increased dendritic branching. 
      However, in co-cultures with OLs, neuronal defects became more apparent, showing 
      cellular hypertrophy and increased axonal density. In addition, TSC neuron-OL 
      co-cultures showed increased OL cell proliferation and decreased OL maturation. 
      Pharmacological intervention with the mTOR regulator rapamycin suppressed these 
      defects. Our patient iPSC-based model, therefore, shows a complex cellular TSC 
      phenotype arising from the interaction of neuronal and glial cells and provides a 
      platform for TSC disease modeling and drug development.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Nadadhur, Aishwarya G
AU  - Nadadhur AG
AD  - Department of Functional Genomics, Center for Neurogenomics and Cognitive 
      Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 
      HV, the Netherlands.
FAU - Alsaqati, Mouhamed
AU  - Alsaqati M
AD  - Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn 
      Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
FAU - Gasparotto, Lisa
AU  - Gasparotto L
AD  - Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, Amsterdam 
      Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands.
FAU - Cornelissen-Steijger, Paulien
AU  - Cornelissen-Steijger P
AD  - Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, Amsterdam 
      Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands.
FAU - van Hugte, Eline
AU  - van Hugte E
AD  - Department of Functional Genomics, Center for Neurogenomics and Cognitive 
      Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 
      HV, the Netherlands.
FAU - Dooves, Stephanie
AU  - Dooves S
AD  - Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, Amsterdam 
      Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands.
FAU - Harwood, Adrian J
AU  - Harwood AJ
AD  - Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn 
      Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
FAU - Heine, Vivi M
AU  - Heine VM
AD  - Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, Amsterdam 
      Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, the Netherlands; 
      Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive 
      Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 1081 
      HV, the Netherlands. Electronic address: vm.heine@vumc.nl.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 100202/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181220
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
SB  - IM
MH  - Action Potentials
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology
MH  - Neuronal Outgrowth
MH  - Neurons/cytology/*physiology
MH  - Oligodendroglia/cytology/*physiology
MH  - Phenotype
MH  - Tuberous Sclerosis/*pathology
PMC - PMC6335594
OTO - NOTNLM
OT  - autism
OT  - co-culture
OT  - glia
OT  - iPSC
OT  - in vitro model
OT  - myelin
OT  - neuron
OT  - neuronal activity
OT  - oligodendrocyte
OT  - tuberous sclerosis complex
EDAT- 2018/12/26 06:00
MHDA- 2020/02/28 06:00
PMCR- 2018/12/20
CRDT- 2018/12/25 06:00
PHST- 2018/03/16 00:00 [received]
PHST- 2018/11/21 00:00 [revised]
PHST- 2018/11/22 00:00 [accepted]
PHST- 2018/12/26 06:00 [pubmed]
PHST- 2020/02/28 06:00 [medline]
PHST- 2018/12/25 06:00 [entrez]
PHST- 2018/12/20 00:00 [pmc-release]
AID - S2213-6711(18)30488-0 [pii]
AID - 10.1016/j.stemcr.2018.11.019 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2019 Jan 8;12(1):42-56. doi: 10.1016/j.stemcr.2018.11.019. 
      Epub 2018 Dec 20.