Wang Kuang-Tse, Chen Yu-Chia, Tsai Fu-Yu, Judy Catherine P, Adler Carolyn E
bioRxiv. 2025 Apr 16:2025.04.14.648795. doi: 10.1101/2025.04.14.648795.
Whole-body regeneration requires adult stem cells with high plasticity to differentiate into missing cell types. Planarians possess a unique configuration of organs embedded in a vast pool of pluripotent stem cells. How stem cells integrate positional information with discrete fates remains unknown. Here, we use the planarian pharynx to define the cell fates that depend on the pioneer transcription factor FoxA. We find that Roundabout receptor RoboA suppresses aberrant pharynx cell fates by altering expression, independent of the canonical ligand Slit. An RNAi screen for extracellular proteins identifies Anosmin-1 as a potential partner of RoboA. Perturbing global patterning demonstrates that / functions locally in the brain. By contrast, altering pharynx fate with knockdown induces head-specific neurons in the pharynx, indicating a latent plasticity of stem cells. Our data links critical extracellular cues with cell fate decisions of highly plastic stem cells, ensuring the fidelity of organ regeneration.
全身再生需要具有高可塑性的成体干细胞分化为缺失的细胞类型。涡虫拥有独特的器官结构，这些器官嵌入大量多能干细胞池中。干细胞如何将位置信息与离散的命运整合仍不清楚。在这里，我们利用涡虫咽来定义依赖先驱转录因子FoxA的细胞命运。我们发现Roundabout受体RoboA通过改变表达来抑制异常的咽细胞命运，这与经典配体Slit无关。对细胞外蛋白进行的RNA干扰筛选确定Anosmin-1为RoboA的潜在伙伴。干扰整体模式表明，/在大脑中局部发挥作用。相比之下，通过敲低改变咽命运会在咽中诱导头部特异性神经元，这表明干细胞具有潜在的可塑性。我们的数据将关键的细胞外信号与高可塑性干细胞的细胞命运决定联系起来，确保器官再生的准确性。
