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Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors.

Lau, Shong LU ; Rylander, Daniella LU ; Jakobsson, Johan LU and Parmar, Malin LU (2014) In Cell Reports 9(5). p.1673-1680
Abstract
Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and... (More)
Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
9
issue
5
pages
1673 - 1680
publisher
Cell Press
external identifiers
  • pmid:25482564
  • wos:000346851900013
  • scopus:84915749642
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.11.017
language
English
LU publication?
yes
id
14515893-893a-45a8-a47f-a019df119196 (old id 4908805)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25482564?dopt=Abstract
date added to LUP
2015-01-10 13:29:39
date last changed
2017-04-09 03:55:17
@article{14515893-893a-45a8-a47f-a019df119196,
  abstract     = {Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy.},
  author       = {Lau, Shong and Rylander, Daniella and Jakobsson, Johan and Parmar, Malin},
  issn         = {2211-1247},
  language     = {eng},
  number       = {5},
  pages        = {1673--1680},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors.},
  url          = {http://dx.doi.org/10.1016/j.celrep.2014.11.017},
  volume       = {9},
  year         = {2014},
}