Essential and dual effects of Notch activity on a natural transdifferentiation event
Abstract Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why some cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans herma...
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Nature Portfolio
2025-01-01
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Online Access: | https://doi.org/10.1038/s41467-024-55286-8 |
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author | Thomas Daniele Jeanne Cury Marie-Charlotte Morin Arnaud Ahier Davide Isaia Sophie Jarriault |
author_facet | Thomas Daniele Jeanne Cury Marie-Charlotte Morin Arnaud Ahier Davide Isaia Sophie Jarriault |
author_sort | Thomas Daniele |
collection | DOAJ |
description | Abstract Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why some cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans hermaphrodites. Endogenous Notch signalling endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Olig and sem-4/Sall). Strikingly, ectopic Notch can trigger additional transdifferentiation in vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate. |
format | Article |
id | doaj-art-02455632e75743b59a279054f3ca9297 |
institution | Kabale University |
issn | 2041-1723 |
language | English |
publishDate | 2025-01-01 |
publisher | Nature Portfolio |
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series | Nature Communications |
spelling | doaj-art-02455632e75743b59a279054f3ca92972025-01-05T12:37:23ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55286-8Essential and dual effects of Notch activity on a natural transdifferentiation eventThomas Daniele0Jeanne Cury1Marie-Charlotte Morin2Arnaud Ahier3Davide Isaia4Sophie Jarriault5Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgDepartment of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgDepartment of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgDepartment of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgDepartment of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgDepartment of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de StrasbourgAbstract Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why some cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans hermaphrodites. Endogenous Notch signalling endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Olig and sem-4/Sall). Strikingly, ectopic Notch can trigger additional transdifferentiation in vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate.https://doi.org/10.1038/s41467-024-55286-8 |
spellingShingle | Thomas Daniele Jeanne Cury Marie-Charlotte Morin Arnaud Ahier Davide Isaia Sophie Jarriault Essential and dual effects of Notch activity on a natural transdifferentiation event Nature Communications |
title | Essential and dual effects of Notch activity on a natural transdifferentiation event |
title_full | Essential and dual effects of Notch activity on a natural transdifferentiation event |
title_fullStr | Essential and dual effects of Notch activity on a natural transdifferentiation event |
title_full_unstemmed | Essential and dual effects of Notch activity on a natural transdifferentiation event |
title_short | Essential and dual effects of Notch activity on a natural transdifferentiation event |
title_sort | essential and dual effects of notch activity on a natural transdifferentiation event |
url | https://doi.org/10.1038/s41467-024-55286-8 |
work_keys_str_mv | AT thomasdaniele essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent AT jeannecury essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent AT mariecharlottemorin essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent AT arnaudahier essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent AT davideisaia essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent AT sophiejarriault essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent |