PMID- 28506534
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20240326
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 8
IP  - 6
DP  - 2017 Jun 6
TI  - NEUROD1 Instructs Neuronal Conversion in Non-Reactive Astrocytes.
PG  - 1506-1515
LID - S2213-6711(17)30167-4 [pii]
LID - 10.1016/j.stemcr.2017.04.013 [doi]
AB  - Currently, all methods for converting non-neuronal cells into neurons involve 
      injury to the brain; however, whether neuronal transdifferentiation can occur 
      long after the period of insult remains largely unknown. Here, we use the 
      transcription factor NEUROD1, previously shown to convert reactive glial cells to 
      neurons in the cortex, to determine whether astrocyte-to-neuron 
      transdifferentiation can occur under physiological conditions. We utilized 
      adeno-associated virus 9 (AAV9), which crosses the blood-brain barrier without 
      injury, to deliver NEUROD1 to astrocytes through an intravascular route. 
      Interestingly, we found that a small, but significant number of non-reactive 
      astrocytes converted to neurons in the striatum, but not the cortex. Moreover, 
      astrocytes cultured to minimize their proliferative potential also exhibited 
      limited neuronal transdifferentiation with NEUROD1 expression. Our results show 
      that a single transcription factor can induce astrocyte-to-neuron conversion 
      under physiological conditions, potentially facilitating future clinical 
      approaches long after the acute injury phase.
CI  - Published by Elsevier Inc.
FAU - Brulet, Rebecca
AU  - Brulet R
AD  - Departments of Molecular Biology, Neurology and Neurotherapeutics, and Hamon 
      Center for Regenerative Science and Medicine, UT Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Matsuda, Taito
AU  - Matsuda T
AD  - Stem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, 
      Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
FAU - Zhang, Ling
AU  - Zhang L
AD  - Departments of Molecular Biology, Neurology and Neurotherapeutics, and Hamon 
      Center for Regenerative Science and Medicine, UT Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Miranda, Carlos
AU  - Miranda C
AD  - Center for Gene Therapy, The Research Institute at Nationwide Children's 
      Hospital, Columbus, OH 43205, USA.
FAU - Giacca, Mauro
AU  - Giacca M
AD  - International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 
      34149 Trieste, Italy.
FAU - Kaspar, Brian K
AU  - Kaspar BK
AD  - Center for Gene Therapy, The Research Institute at Nationwide Children's 
      Hospital, Columbus, OH 43205, USA; Departments of Neuroscience and Pediatrics, 
      The Ohio State University, Columbus, OH 43210, USA.
FAU - Nakashima, Kinichi
AU  - Nakashima K
AD  - Stem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, 
      Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
FAU - Hsieh, Jenny
AU  - Hsieh J
AD  - Departments of Molecular Biology, Neurology and Neurotherapeutics, and Hamon 
      Center for Regenerative Science and Medicine, UT Southwestern Medical Center, 
      Dallas, TX 75390, USA. Electronic address: jenny.hsieh@utsouthwestern.edu.
LA  - eng
GR  - R01 NS089770/NS/NINDS NIH HHS/United States
GR  - R01 NS093992/NS/NINDS NIH HHS/United States
GR  - T32 GM083831/GM/NIGMS NIH HHS/United States
GR  - R01 NS081203/NS/NINDS NIH HHS/United States
GR  - K02 AG041815/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170511
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 169238-82-8 (Neurogenic differentiation factor 1)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/*metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism
MH  - Blood-Brain Barrier/metabolism
MH  - Cell Differentiation
MH  - Cell Transdifferentiation
MH  - Cells, Cultured
MH  - Cellular Reprogramming
MH  - Corpus Striatum/metabolism
MH  - Dependovirus/genetics
MH  - Genetic Vectors/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/cytology/*metabolism
MH  - Rats
PMC - PMC5470076
OTO - NOTNLM
OT  - AAV9
OT  - NeuroD
OT  - astrocytes
OT  - cortex
OT  - neurons
OT  - reprogramming
OT  - striatum
OT  - transdifferentiation
EDAT- 2017/05/17 06:00
MHDA- 2018/01/30 06:00
PMCR- 2017/05/11
CRDT- 2017/05/17 06:00
PHST- 2016/09/02 00:00 [received]
PHST- 2017/04/11 00:00 [revised]
PHST- 2017/04/12 00:00 [accepted]
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
PHST- 2017/05/17 06:00 [entrez]
PHST- 2017/05/11 00:00 [pmc-release]
AID - S2213-6711(17)30167-4 [pii]
AID - 10.1016/j.stemcr.2017.04.013 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2017 Jun 6;8(6):1506-1515. doi: 10.1016/j.stemcr.2017.04.013. 
      Epub 2017 May 11.