Highly efficient generation of induced neurons from human fibroblasts that survive transplantation into the adult rat brain.
Pereira, Maria J M LU ; Pfisterer, Ulrich LU ; Rylander, Daniella LU ; Torper, Olof LU ; Lau, Shong LU ; Lundblad, Martin LU ; Grealish, Shane LU and Parmar, Malin LU
(2014)
In Scientific Reports
4.
- Abstract
- Induced neurons (iNs) offer a novel source of human neurons that can be explored for applications of disease modelling, diagnostics, drug screening and cell replacement therapy. Here we present a protocol for highly efficient generation of functional iNs from fetal human fibroblasts, and also demonstrate the ability of these converted human iNs (hiNs) to survive transplantation and maintain their phenotype in the adult rat brain. The protocol encompasses a delay in transgene activation after viral transduction that resulted in a significant increase in conversion efficiency. Combining this approach with treatment of small molecules that inhibit SMAD signalling and activate WNT signalling provides a further increase in the conversion... (More)
- Induced neurons (iNs) offer a novel source of human neurons that can be explored for applications of disease modelling, diagnostics, drug screening and cell replacement therapy. Here we present a protocol for highly efficient generation of functional iNs from fetal human fibroblasts, and also demonstrate the ability of these converted human iNs (hiNs) to survive transplantation and maintain their phenotype in the adult rat brain. The protocol encompasses a delay in transgene activation after viral transduction that resulted in a significant increase in conversion efficiency. Combining this approach with treatment of small molecules that inhibit SMAD signalling and activate WNT signalling provides a further increase in the conversion efficiency and neuronal purity, resulting in a protocol that provides a highly efficient method for the generation of large numbers of functional and transplantable iNs from human fibroblasts without the use of a selection step. When transplanting the converted neurons from different stages of in vitro culture into the brain of adult rats, we observed robust survival and maintenance of neuronal identity four weeks post-transplantation. Interestingly, the positive effect of small molecule treatment observed in vitro did not result in a higher yield of iNs surviving transplantation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4691910
- author
- Pereira, Maria J M
LU
; Pfisterer, Ulrich
LU
; Rylander, Daniella
LU
; Torper, Olof
LU
; Lau, Shong
LU
; Lundblad, Martin
LU
; Grealish, Shane
LU
and Parmar, Malin
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 4
- article number
- 6330
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:25208484
- wos:000341934500004
- scopus:84915734112
- pmid:25208484
- ISSN
- 2045-2322
- DOI
- 10.1038/srep06330
- project
- Cell reprogramming: a new method for generating functional neurons
- language
- English
- LU publication?
- yes
- id
- 6cd741e6-ada8-4ffd-92d2-75fe2d28c32b (old id 4691910)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25208484?dopt=Abstract
- date added to LUP
- 2016-04-01 14:32:32
- date last changed
- 2022-03-22 00:34:44
@article{6cd741e6-ada8-4ffd-92d2-75fe2d28c32b,
abstract = {{Induced neurons (iNs) offer a novel source of human neurons that can be explored for applications of disease modelling, diagnostics, drug screening and cell replacement therapy. Here we present a protocol for highly efficient generation of functional iNs from fetal human fibroblasts, and also demonstrate the ability of these converted human iNs (hiNs) to survive transplantation and maintain their phenotype in the adult rat brain. The protocol encompasses a delay in transgene activation after viral transduction that resulted in a significant increase in conversion efficiency. Combining this approach with treatment of small molecules that inhibit SMAD signalling and activate WNT signalling provides a further increase in the conversion efficiency and neuronal purity, resulting in a protocol that provides a highly efficient method for the generation of large numbers of functional and transplantable iNs from human fibroblasts without the use of a selection step. When transplanting the converted neurons from different stages of in vitro culture into the brain of adult rats, we observed robust survival and maintenance of neuronal identity four weeks post-transplantation. Interestingly, the positive effect of small molecule treatment observed in vitro did not result in a higher yield of iNs surviving transplantation.}},
author = {{Pereira, Maria J M and Pfisterer, Ulrich and Rylander, Daniella and Torper, Olof and Lau, Shong and Lundblad, Martin and Grealish, Shane and Parmar, Malin}},
issn = {{2045-2322}},
language = {{eng}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Highly efficient generation of induced neurons from human fibroblasts that survive transplantation into the adult rat brain.}},
url = {{https://lup.lub.lu.se/search/files/4030481/5309215.pdf}},
doi = {{10.1038/srep06330}},
volume = {{4}},
year = {{2014}},
}