Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis.
Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis.
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DOI：
10.7554/elife.29312
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发表时间：
2018-03-20
期刊：
影响因子：
7.7
通讯作者：
Lancrin C
中科院分区：
文献类型：
--
作者：
Bergiers I;Andrews T;Vargel Bölükbaşı Ö;Buness A;Janosz E;Lopez-Anguita N;Ganter K;Kosim K;Celen C;Itır Perçin G;Collier P;Baying B;Benes V;Hemberg M;Lancrin C
单细胞转录组学技术的最新进展为在单细胞水平上研究基因调控网络（grn）打开了大门。在这里，我们使用单细胞转录组分析的组合研究了控制小鼠胚胎内皮造血干细胞和祖细胞出现的grn。我们发现七种转录因子（Runx1, Gata2, Tal1, Fli1, Lyl1， Erg和Lmo2）在表达内皮和造血标志物的中间群体中特异性共表达。在heptad中，我们发现了两组功能相反的因子：一组（Erg/Fli1）促进内皮细胞的命运，另一组（Runx1/Gata2）促进造血的命运。令人惊讶的是，我们的数据表明，尽管Fli1最初支持内皮细胞的命运，但当它与Runx1共表达时，它获得了促造血的作用。这项工作证明了单细胞rna测序在表征复杂转录因子动力学方面的力量。
Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.