Small molecules increase direct neural conversion of human fibroblasts
Pfisterer, Ulrich LU ; Ek, Fredrik LU ; Lang, Stefan LU
; Soneji, Shamit
LU
; Olsson, Roger
LU
and Parmar, Malin
LU
(2016)
In Scientific Reports
6.
- Abstract
The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening assay for small molecules that increase the conversion efficiency. Using this assay, we screened 307 compounds from five annotated libraries and identified six compounds that were very potent in potentiating the reprogramming process. When combined in an optimal combination and dose, these compounds increased the reprogramming efficiency of human... (More)
The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening assay for small molecules that increase the conversion efficiency. Using this assay, we screened 307 compounds from five annotated libraries and identified six compounds that were very potent in potentiating the reprogramming process. When combined in an optimal combination and dose, these compounds increased the reprogramming efficiency of human fibroblasts more than 6-fold. Global gene expression and CellNet analysis at different timepoints during the reprogramming process revealed that neuron-specific genes and gene regulatory networks (GRNs) became progressively more activated while converting cells shut down fibroblast-specific GRNs. Further bioinformatics analysis revealed that the addition of the six compound resulted in the accelerated upregulation of a subset of neuronal genes, and also increased expression of genes associated with transcriptional activity and mediation of cellular stress response.
(Less)
- author
- Pfisterer, Ulrich
LU
; Ek, Fredrik
LU
; Lang, Stefan
LU
; Soneji, Shamit
LU
; Olsson, Roger
LU
and Parmar, Malin
LU
- organization
- publishing date
- 2016-12-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 6
- article number
- 38290
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85003904916
- pmid:27917895
- wos:000389184000001
- ISSN
- 2045-2322
- DOI
- 10.1038/srep38290
- language
- English
- LU publication?
- yes
- id
- 9a630a69-552b-4a9a-9ff6-8b65b39b9eba
- date added to LUP
- 2016-12-23 10:47:26
- date last changed
- 2024-04-05 12:03:49
@article{9a630a69-552b-4a9a-9ff6-8b65b39b9eba,
abstract = {{<p>The generation of human induced neurons (hiNs) via exogenous delivery of neural transcription factors represents a novel technique to obtain disease and patient specific neurons. These cells have the potential to be used for disease modeling, diagnostics and drug screening, and also to be further developed for brain repair. In the present study, we utilized hiNs to develop an unbiased screening assay for small molecules that increase the conversion efficiency. Using this assay, we screened 307 compounds from five annotated libraries and identified six compounds that were very potent in potentiating the reprogramming process. When combined in an optimal combination and dose, these compounds increased the reprogramming efficiency of human fibroblasts more than 6-fold. Global gene expression and CellNet analysis at different timepoints during the reprogramming process revealed that neuron-specific genes and gene regulatory networks (GRNs) became progressively more activated while converting cells shut down fibroblast-specific GRNs. Further bioinformatics analysis revealed that the addition of the six compound resulted in the accelerated upregulation of a subset of neuronal genes, and also increased expression of genes associated with transcriptional activity and mediation of cellular stress response.</p>}},
author = {{Pfisterer, Ulrich and Ek, Fredrik and Lang, Stefan and Soneji, Shamit and Olsson, Roger and Parmar, Malin}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Small molecules increase direct neural conversion of human fibroblasts}},
url = {{http://dx.doi.org/10.1038/srep38290}},
doi = {{10.1038/srep38290}},
volume = {{6}},
year = {{2016}},
}