Phospholipase Cβ1 is activated by Gαq to generate calcium signals in response to hormones and neurotransmitters. Besides carrying out this plasma membrane function, PLCβ1 has a cytosolic population that helps to drive the differentiation of PC12 cells by inhibiting a nuclease that promotes RNA‐induced silencing (C3PO). Here, we show that down‐regulating PLCβ1 or reducing its cytosolic population by activating Gαq to localize it to the plasma membrane returns differentiated PC12 and SK‐N‐SH cells to an undifferentiated state. In this state, PC12 cells have a spherical morphology, resume proliferation, and express the stem cell transcription factors nanog and Oct4. Similar changes are seen when C3PO is down‐regulated. This return to a stem‐like state is accompanied by shifts in multiple miR populations. Surprisingly, de‐differentiation can be induced by extended stimulation of Gαq where cells return to a spherical morphology and levels of specific miRs return to their undifferentiated values. In complementary studies, we followed the real‐time hydrolysis of a fluorescent‐tagged miR in cells where PLCβ1 or C3PO were down‐regulated in PC12 cells and find substantial differences in miR processing in the undifferentiated and differentiated states. Taken together, our studies suggest that PLCβ1, through its ability to regulate C3PO and endogenous miR populations, mediates the differentiation of two types of cultured neuronal cells.

中文翻译：

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Gαq/磷脂酶 Cβ1 信号通路的刺激使分化细胞恢复到干细胞样状态

磷脂酶 Cβ1 被 Gαq 激活以产生钙信号以响应激素和神经递质。除了执行这种质膜功能外，PLCβ1 还具有一个胞质群，通过抑制促进 RNA 诱导的沉默 (C3PO) 的核酸酶来帮助驱动 PC12 细胞的分化。在这里，我们展示了下调 PLCβ1 或通过激活 Gαq 将其定位到质膜来减少其胞浆数量，使分化的 PC12 和 SK-N-SH 细胞恢复到未分化状态。在这种状态下，PC12 细胞具有球形形态，恢复增殖，并表达干细胞转录因子 nanog 和 Oct4。当 C3PO 被下调时，也会出现类似的变化。这种回到茎状状态的过程伴随着多个 miR 种群的变化。出奇，去分化可以通过对 Gαq 的延长刺激来诱导，其中细胞恢复到球形形态并且特定 miR 的水平恢复到其未分化值。在补充研究中，我们跟踪荧光标记的 miR 在 PC12 细胞中 PLCβ1 或 C3PO 被下调的细胞中的实时水解，发现未分化和分化状态下 miR 加工的显着差异。总之，我们的研究表明，PLCβ1 通过其调节 C3PO 和内源性 miR 群体的能力，介导两种培养的神经元细胞的分化。我们跟踪了荧光标记的 miR 在 PC12 细胞中 PLCβ1 或 C3PO 被下调的细胞中的实时水解，发现在未分化和分化状态下 miR 加工存在显着差异。总之，我们的研究表明，PLCβ1 通过其调节 C3PO 和内源性 miR 群体的能力，介导两种培养的神经元细胞的分化。我们跟踪了荧光标记的 miR 在 PC12 细胞中 PLCβ1 或 C3PO 被下调的细胞中的实时水解，发现在未分化和分化状态下 miR 加工存在显着差异。总之，我们的研究表明，PLCβ1 通过其调节 C3PO 和内源性 miR 群体的能力，介导两种培养的神经元细胞的分化。