Cargando…
Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons
Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cell̀s identity and if the cell fate definin...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374837/ https://www.ncbi.nlm.nih.gov/pubmed/22719915 http://dx.doi.org/10.1371/journal.pone.0038651 |
_version_ | 1782235692666978304 |
---|---|
author | Thoma, Eva C. Wischmeyer, Erhard Offen, Nils Maurus, Katja Sirén, Anna-Leena Schartl, Manfred Wagner, Toni U. |
author_facet | Thoma, Eva C. Wischmeyer, Erhard Offen, Nils Maurus, Katja Sirén, Anna-Leena Schartl, Manfred Wagner, Toni U. |
author_sort | Thoma, Eva C. |
collection | PubMed |
description | Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cell̀s identity and if the cell fate defining potential of TFs is also operative in pluripotent stem cells in vitro. Here, we show that ectopic expression of the neural TF Neurogenin2 (Ngn2) is sufficient to induce rapid and efficient differentiation of embryonic stem cells (ESCs) into mature glutamatergic neurons. Ngn2-induced neuronal differentiation did not require any additional external or internal factors and occurred even under pluripotency-promoting conditions. Differentiated cells displayed neuron-specific morphology, protein expression, and functional features, most importantly the generation of action potentials and contacts with hippocampal neurons. Gene expression analyses revealed that Ngn2-induced in vitro differentiation partially resembled neurogenesis in vivo, as it included specific activation of Ngn2 target genes and interaction partners. These findings demonstrate that a single gene is sufficient to determine cell fate decisions of uncommitted stem cells thus giving insights into the role of key developmental genes during lineage commitment. Furthermore, we present a promising tool to improve directed differentiation strategies for applications in both stem cell research and regenerative medicine. |
format | Online Article Text |
id | pubmed-3374837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33748372012-06-20 Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons Thoma, Eva C. Wischmeyer, Erhard Offen, Nils Maurus, Katja Sirén, Anna-Leena Schartl, Manfred Wagner, Toni U. PLoS One Research Article Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cell̀s identity and if the cell fate defining potential of TFs is also operative in pluripotent stem cells in vitro. Here, we show that ectopic expression of the neural TF Neurogenin2 (Ngn2) is sufficient to induce rapid and efficient differentiation of embryonic stem cells (ESCs) into mature glutamatergic neurons. Ngn2-induced neuronal differentiation did not require any additional external or internal factors and occurred even under pluripotency-promoting conditions. Differentiated cells displayed neuron-specific morphology, protein expression, and functional features, most importantly the generation of action potentials and contacts with hippocampal neurons. Gene expression analyses revealed that Ngn2-induced in vitro differentiation partially resembled neurogenesis in vivo, as it included specific activation of Ngn2 target genes and interaction partners. These findings demonstrate that a single gene is sufficient to determine cell fate decisions of uncommitted stem cells thus giving insights into the role of key developmental genes during lineage commitment. Furthermore, we present a promising tool to improve directed differentiation strategies for applications in both stem cell research and regenerative medicine. Public Library of Science 2012-06-13 /pmc/articles/PMC3374837/ /pubmed/22719915 http://dx.doi.org/10.1371/journal.pone.0038651 Text en Thoma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Thoma, Eva C. Wischmeyer, Erhard Offen, Nils Maurus, Katja Sirén, Anna-Leena Schartl, Manfred Wagner, Toni U. Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title | Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title_full | Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title_fullStr | Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title_full_unstemmed | Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title_short | Ectopic Expression of Neurogenin 2 Alone is Sufficient to Induce Differentiation of Embryonic Stem Cells into Mature Neurons |
title_sort | ectopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374837/ https://www.ncbi.nlm.nih.gov/pubmed/22719915 http://dx.doi.org/10.1371/journal.pone.0038651 |
work_keys_str_mv | AT thomaevac ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT wischmeyererhard ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT offennils ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT mauruskatja ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT sirenannaleena ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT schartlmanfred ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT wagnertoniu ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons |