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Peer-reviewedCC BY 4.0PLOS Genetics

The SynMuvA lin-15A licenses natural transdifferentiation by antagonizing identity safeguarding mechanisms

  • Sarah Frieda Becker1
  • Marie-Charlotte Morin2
  • Julien Lambert3
  • Shashi Kumar Suman4
  • Francesco Nicola Carelli5
  • Alex Appert
  • Stéphane Roth
  • Sarah Hoff-Yoessle
  • Jessica D. Medina-Sanchez
  • Manuela Portoso
  • Julie Ahringer
  • Sophie Jarriault
5 affiliations
  1. 1Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U1298, Université de Strasbourg, Illkirch, France
  2. 2Current address: Biozentrum, University of Basel, Basel, Switzerland
  3. 3The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom
  4. 4Current address: Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
  5. 5Institut Curie, INSERM U934/CNRS UMR 3215, Paris Sciences et Lettres Research University, Sorbonne University, Paris, France
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Abstract

The mechanisms that restrict or enable latent cellular plasticity have attracted growing interest over the past decade, with important implications for cancer and regenerative therapies. However, the diversity of both pro- and anti-plasticity mechanisms remains incompletely understood. Here, we identify the THAP domain gene lin-15A as a novel factor involved in the natural rectal-to-neuronal Y-to-PDA transdifferentiation in Caenorhabditis elegans. Our genetic analyses show that lin-15A acts in parallel to previously described plasticity factors. Null mutant suggests that, rather than driving the process, LIN-15A licenses its initiation by antagonizing several chromatin-modifying complexes known to safeguard differentiated cell identities. In addition, our data show that even cells developmentally programmed to undergo transdifferentiation exhibit reprogramming barriers. Interestingly, lin-15A is not a core plasticity factor per se but acts as one specifically in the Y cell context. Together, our findings support a model in which diverse molecular activities coordinate controlled cell identity conversions: plasticity factors function as Drivers, while others like lin-15A, termed here transdifferentiation Licensers, attenuate identity safeguarding mechanisms, thereby facilitating transdifferentiation.

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Cite

BibTeXRIS
BibTeX
@article{becker2026synmuva,
  title = {{The SynMuvA lin-15A licenses natural transdifferentiation by antagonizing identity safeguarding mechanisms}},
  author = {Sarah Frieda Becker and Marie-Charlotte Morin and Julien Lambert and Shashi Kumar Suman and Francesco Nicola Carelli and Alex Appert and Stéphane Roth and Sarah Hoff-Yoessle and Jessica D. Medina-Sanchez and Manuela Portoso and Julie Ahringer and Sophie Jarriault},
  journal = {PLOS Genetics},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pgen.1012290},
  url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012290},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The SynMuvA lin-15A licenses natural transdifferentiation by antagonizing identity safeguarding mechanisms
AU  - Sarah Frieda Becker
AU  - Marie-Charlotte Morin
AU  - Julien Lambert
AU  - Shashi Kumar Suman
AU  - Francesco Nicola Carelli
AU  - Alex Appert
AU  - Stéphane Roth
AU  - Sarah Hoff-Yoessle
AU  - Jessica D. Medina-Sanchez
AU  - Manuela Portoso
AU  - Julie Ahringer
AU  - Sophie Jarriault
PY  - 2026
DA  - 2026/09/25
JO  - PLOS Genetics
DO  - 10.1371/journal.pgen.1012290
UR  - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012290
AB  - The mechanisms that restrict or enable latent cellular plasticity have attracted growing interest over the past decade, with important implications for cancer and regenerative therapies. However, the diversity of both pro- and anti-plasticity mechanisms remains incompletely understood. Here, we identify the THAP domain gene lin-15A as a novel factor involved in the natural rectal-to-neuronal Y-to-PDA transdifferentiation in Caenorhabditis elegans. Our genetic analyses show that lin-15A acts in parallel to previously described plasticity factors. Null mutant suggests that, rather than driving the process, LIN-15A licenses its initiation by antagonizing several chromatin-modifying complexes known to safeguard differentiated cell identities. In addition, our data show that even cells developmentally programmed to undergo transdifferentiation exhibit reprogramming barriers. Interestingly, lin-15A is not a core plasticity factor per se but acts as one specifically in the Y cell context. Together, our findings support a model in which diverse molecular activities coordinate controlled cell identity conversions: plasticity factors function as Drivers, while others like lin-15A, termed here transdifferentiation Licensers, attenuate identity safeguarding mechanisms, thereby facilitating transdifferentiation.
SN  - 1553-7404
SN  - 1553-7390
ER  -