PRDM1 controls the sequential activation of neural, neural crest and sensory progenitor determinants
PRDM1 controls the sequential activation of neural, neural crest and sensory progenitor determinants
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DOI：
10.1242/dev.181107
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发表时间：
2019-12-15
期刊：
影响因子：
4.6
通讯作者：
Streit, Andrea
中科院分区：
文献类型：
--
作者：
Prajapati, Ravindra S.;Hintze, Mark;Streit, Andrea
在早期胚胎发生过程中，外胚层迅速细分为神经、神经嵴和感觉祖细胞。谱系决定簇的发生和多能性标记的丧失如何在体内时间和空间上协调仍有争议。在这里，我们确定了一个至关重要的作用，转录因子PRDM1在有序的过渡，从上胚层定义的神经谱系鸡。PRDM1最初在整个上胚层中广泛表达，但随着细胞命运的指定而逐渐受到限制。我们发现，PRDM1是所需的一些多能性标志物的损失和神经，神经嵴和感觉祖细胞特异性基因的发病。PRDM1通过与其启动子区域结合并募集组蛋白去甲基化酶Kdm4a以去除抑制性组蛋白标记来直接激活其表达。然而，一旦神经谱系决定因素表达，它们反过来抑制PRDM1，而长期的PRDM1表达抑制神经，神经嵴和感觉祖基因，这表明其下调是必要的细胞保持其身份。因此，PROM1在外胚层细胞命运分配过程中起着多种作用。
During early embryogenesis, the ectoderm is rapidly subdivided into neural, neural crest and sensory progenitors. How the onset of lineage determinants and the loss of pluripotency markers are temporally and spatially coordinated in vivo is still debated. Here, we identify a crucial role for the transcription factor PRDM1 in the orderly transition from epiblast to defined neural lineages in chick. PRDM1 is initially expressed broadly in the entire epiblast, but becomes gradually restricted as cell fates are specified. We find that PRDM1 is required for the loss of some pluripotency markers and the onset of neural, neural crest and sensory progenitor specifier genes. PRDM1 directly activates their expression by binding to their promoter regions and recruiting the histone demethylase Kdm4a to remove repressive histone marks. However, once neural lineage determinants become expressed, they in turn repress PRDM1, whereas prolonged PRDM1 expression inhibits neural, neural crest and sensory progenitor genes, suggesting that its downregulation is necessary for cells to maintain their identity. Therefore, PROM1 plays multiple roles during ectodermal cell fate allocation.