Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons
Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/15477 |
| _version_ | 1811180648309719040 |
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| author | Stefanie Seelk Irene Adrian-Kalchhauser Balázs Hargitai Martina Hajduskova Silvia Gutnik Baris Tursun Rafal Ciosk |
| author_facet | Stefanie Seelk Irene Adrian-Kalchhauser Balázs Hargitai Martina Hajduskova Silvia Gutnik Baris Tursun Rafal Ciosk |
| author_sort | Stefanie Seelk |
| collection | DOAJ |
| description | Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling. |
| first_indexed | 2024-04-11T09:05:40Z |
| format | Article |
| id | doaj.art-088ceb473be0425099d226bd509987f5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:40Z |
| publishDate | 2016-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-088ceb473be0425099d226bd509987f52022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-09-01510.7554/eLife.15477Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neuronsStefanie Seelk0Irene Adrian-Kalchhauser1Balázs Hargitai2Martina Hajduskova3Silvia Gutnik4Baris Tursun5https://orcid.org/0000-0001-7293-8629Rafal Ciosk6https://orcid.org/0000-0003-2234-6216Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyFriedrich Miescher Institute for Biomedical Research, Basel, SwitzerlandFriedrich Miescher Institute for Biomedical Research, Basel, SwitzerlandBerlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyFriedrich Miescher Institute for Biomedical Research, Basel, SwitzerlandBerlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyFriedrich Miescher Institute for Biomedical Research, Basel, SwitzerlandCell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling.https://elifesciences.org/articles/15477NotchPRC2reprogramingutx-1glp-1mes-2 |
| spellingShingle | Stefanie Seelk Irene Adrian-Kalchhauser Balázs Hargitai Martina Hajduskova Silvia Gutnik Baris Tursun Rafal Ciosk Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons eLife Notch PRC2 reprograming utx-1 glp-1 mes-2 |
| title | Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons |
| title_full | Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons |
| title_fullStr | Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons |
| title_full_unstemmed | Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons |
| title_short | Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons |
| title_sort | increasing notch signaling antagonizes prc2 mediated silencing to promote reprograming of germ cells into neurons |
| topic | Notch PRC2 reprograming utx-1 glp-1 mes-2 |
| url | https://elifesciences.org/articles/15477 |
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