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Ectopic expression of Neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons

Please always quote using this URN: urn:nbn:de:bvb:20-opus-75862
  • 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 cells 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 matureRecent 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 cells 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.show moreshow less

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Metadaten
Author: Eva C. Thoma, Erhard Wischmeyer, Nils Offen, Katja Maurus, Anna-Leena Sirén, Manfred Schartl, Toni U. Wagner
URN:urn:nbn:de:bvb:20-opus-75862
Document Type:Journal article
Faculties:Medizinische Fakultät / Physiologisches Institut
Language:English
Year of Completion:2012
Source:In: PLoS One (2012) 7: 6, doi:10.1371/journal.pone.0038651
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
GND Keyword:Physiologie
Release Date:2013/04/16
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2012
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung