Direct conversion of human fibroblasts to dopaminergic neurons.
(2011) In Proceedings of the National Academy of Sciences 108(25). p.10343-10348- Abstract
- Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2,... (More)
- Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2008394
- author
- Pfisterer, Ulrich LU ; Kirkeby, Agnete LU ; Torper, Olof LU ; Wood, James LU ; Nelander Wahlestedt, Jenny LU ; Dufour, Audrey ; Björklund, Anders LU ; Lindvall, Olle LU ; Jakobsson, Johan LU and Parmar, Malin LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 108
- issue
- 25
- pages
- 10343 - 10348
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000291857500063
- pmid:21646515
- scopus:79959951387
- pmid:21646515
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1105135108
- language
- English
- LU publication?
- yes
- id
- 93b45bd9-f506-40b5-a20b-5adad86564b8 (old id 2008394)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21646515?dopt=Abstract
- date added to LUP
- 2016-04-04 07:30:46
- date last changed
- 2024-02-27 15:50:20
@article{93b45bd9-f506-40b5-a20b-5adad86564b8, abstract = {{Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.}}, author = {{Pfisterer, Ulrich and Kirkeby, Agnete and Torper, Olof and Wood, James and Nelander Wahlestedt, Jenny and Dufour, Audrey and Björklund, Anders and Lindvall, Olle and Jakobsson, Johan and Parmar, Malin}}, issn = {{1091-6490}}, language = {{eng}}, number = {{25}}, pages = {{10343--10348}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{Direct conversion of human fibroblasts to dopaminergic neurons.}}, url = {{http://dx.doi.org/10.1073/pnas.1105135108}}, doi = {{10.1073/pnas.1105135108}}, volume = {{108}}, year = {{2011}}, }