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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719915/pdf/?tool=EBI |
| _version_ | 1818458892635471872 |
|---|---|
| author | Eva C Thoma Erhard Wischmeyer Nils Offen Katja Maurus Anna-Leena Sirén Manfred Schartl Toni U Wagner |
| author_facet | Eva C Thoma Erhard Wischmeyer Nils Offen Katja Maurus Anna-Leena Sirén Manfred Schartl Toni U Wagner |
| author_sort | Eva C Thoma |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T23:05:41Z |
| format | Article |
| id | doaj.art-fe998d4fe3b8401bb62b9082103ad946 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:05:41Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fe998d4fe3b8401bb62b9082103ad9462022-12-21T22:44:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3865110.1371/journal.pone.0038651Ectopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons.Eva C ThomaErhard WischmeyerNils OffenKatja MaurusAnna-Leena SirénManfred SchartlToni U WagnerRecent 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719915/pdf/?tool=EBI |
| spellingShingle | Eva C Thoma Erhard Wischmeyer Nils Offen Katja Maurus Anna-Leena Sirén Manfred Schartl Toni U Wagner Ectopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons. PLoS ONE |
| 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719915/pdf/?tool=EBI |
| work_keys_str_mv | AT evacthoma ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT erhardwischmeyer ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT nilsoffen ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT katjamaurus ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT annaleenasiren ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT manfredschartl ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons AT toniuwagner ectopicexpressionofneurogenin2aloneissufficienttoinducedifferentiationofembryonicstemcellsintomatureneurons |