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...

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Autores principales: Eva C Thoma, Erhard Wischmeyer, Nils Offen, Katja Maurus, Anna-Leena Sirén, Manfred Schartl, Toni U Wagner
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/fe998d4fe3b8401bb62b9082103ad946
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spelling oai:doaj.org-article:fe998d4fe3b8401bb62b9082103ad9462021-11-18T07:15:37ZEctopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons.1932-620310.1371/journal.pone.0038651https://doaj.org/article/fe998d4fe3b8401bb62b9082103ad9462012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719915/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent 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.Eva C ThomaErhard WischmeyerNils OffenKatja MaurusAnna-Leena SirénManfred SchartlToni U WagnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38651 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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.
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 article
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
title 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_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_sort ectopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/fe998d4fe3b8401bb62b9082103ad946
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