Single cell dissection of early kidney development: multilineage priming
Single cell dissection of early kidney development: multilineage priming
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DOI：
10.1242/dev.110601
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发表时间：
2014-08-01
期刊：
影响因子：
4.6
通讯作者：
Potter, S. Steven
中科院分区：
文献类型：
--
作者：
Brunskill, Eric W.;Park, Joo-Seop;Potter, S. Steven
我们使用单个细胞RNA-seq策略在发育中的肾脏中创建基因表达模式的地图集。在肾脏发育的几个阶段，组织学统一的细胞种群产生了多个不同的谱系。我们对E11.5和E12.5的总小鼠肾脏以及P4的肾囊泡进行了单细胞RNA-seq分析。我们定义了主要由基因抑制驱动的祖细胞诱导的早期阶段。在E11.5祖细胞中观察到了与分化细胞类型相关的标记基因的惊人随机表达。我们提供了肾囊泡中已经存在的极化基因表达的全局视图，肾囊泡是肾单位的第一个上皮前体。我们表明，HOX基因读成绩单可以剪接以产生基因间同型互换。我们还确定了具有部分降解的非编码RNA的令人惊讶的基因。也许最有趣的是，在早期发育时期，单细胞通常表达与几种发育途径相关的基因。这提供了有力的证据，表明初始器官发生涉及多素启动过程。接下来是基因抑制的组合，该基因抑制了与大多数可能的谱系相关的基因，以及驱动所选发育方向的基因数量增加的激活。
We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction.