Mouse embryonic stem cells can differentiate via multiple paths to the same state
Mouse embryonic stem cells can differentiate via multiple paths to the same state
复制标题
DOI：
10.7554/elife.26945
复制
发表时间：
2017-10-09
期刊：
影响因子：
7.7
通讯作者：
Krischner, Marc W.
中科院分区：
文献类型：
--
作者：
Briggs, James Alexander;Li, Victor C.;Krischner, Marc W.
在胚胎发育过程中，细胞通过典型的中间状态序列分化产生特定的成熟命运。相比之下，通过异位表达末端转录因子（直接编程）驱动分化可以通过其他途径产生类似的命运。直接编程中的分化与胚胎分化之间的关系尚不清楚。我们应用单细胞RNA测序来比较两种运动神经元分化方案：一种接近胚胎谱系的标准方案和一种直接编程方法。两者最初都经历了类似的早期神经承诺。后来，直接编程路径偏离到一个新的过渡状态，而不是遵循预期的胚胎脊柱中间体。直接编程的新状态具有特异性和非特征性的基因表达。它在基因表达空间中形成一个循环，分别收敛到与标准路径相同的最终运动神经元状态。尽管它们的发育历史不同，但两种方案的运动神经元在结构、功能和转录上都类似于从胚胎中分离出来的运动神经元。
In embryonic development, cells differentiate through stereotypical sequences of intermediate states to generate particular mature fates. By contrast, driving differentiation by ectopically expressing terminal transcription factors (direct programming) can generate similar fates by alternative routes. How differentiation in direct programming relates to embryonic differentiation is unclear. We applied single-cell RNA sequencing to compare two motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method. Both initially undergo similar early neural commitment. Later, the direct programming path diverges into a novel transitional state rather than following the expected embryonic spinal intermediates. The novel state in direct programming has specific and uncharacteristic gene expression. It forms a loop in gene expression space that converges separately onto the same final motor neuron state as the standard path. Despite their different developmental histories, motor neurons from both protocols structurally, functionally, and transcriptionally resemble motor neurons isolated from embryos.