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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Main Authors: Thomas Daniele, Jeanne Cury, Marie-Charlotte Morin, Arnaud Ahier, Davide Isaia, Sophie Jarriault
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
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.
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issn 2041-1723
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publishDate 2025-01-01
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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
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AT arnaudahier essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent
AT davideisaia essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent
AT sophiejarriault essentialanddualeffectsofnotchactivityonanaturaltransdifferentiationevent