Daniele Thomas, Cury Jeanne, Morin Marie-Charlotte, Ahier Arnaud, Isaia Davide, Jarriault Sophie
Department 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.
Vertex Pharmaceuticals (CH) GmbH, Zug, Switzerland.
Nat Commun. 2025 Jan 2;16(1):75. doi: 10.1038/s41467-024-55286-8.
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.
细胞身份可以自然地或通过实验进行重编程，尽管频率很低。为什么有些细胞，而不是它们的邻居，会发生细胞身份转换仍不清楚。我们发现Notch信号在秀丽隐杆线虫雌雄同体中促进自然转分化过程中起关键作用。内源性Notch信号通过促进可塑性因子（hlh-16/Olig和sem-4/Sall）的表达赋予细胞转分化的能力。引人注目的是，异位Notch可以在体内触发额外的转分化。然而，Notch信号根据其激活时间既能促进也能阻断转分化。Notch仅在早期精确的机会窗口期间促进转分化，并且信号持续时间必须在时间上受到严格控制。我们的发现强调了自然细胞重编程启动之前潜在分子事件的时间性和动态性的重要性。最后，我们的结果支持一种模型，即外在信号和内在细胞环境相结合赋予细胞转分化的能力。
