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Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment
PLOS Biology ( IF 9.8 ) Pub Date : 2017-07-27 , DOI: 10.1371/journal.pbio.2001867
Alice Moussy , Jérémie Cosette , Romuald Parmentier , Cindy da Silva , Guillaume Corre , Angélique Richard , Olivier Gandrillon , Daniel Stockholm , András Páldi

Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes in cord blood-derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the 2 stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the 2 phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology, and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process (which is different from a simple binary switch between 2 options, as it is usually envisioned).



中文翻译:

集成的延时和单细胞转录研究突出了人类造血细胞命运承诺的可变性和动态性

各个单元以不一定统一的方式做出沿袭承诺决策。我们通过在单细胞水平上表征脐血来源的CD34 +细胞的转录变化并将数据与细胞分裂历史和通过延时显微镜确定的形态学变化相结合来解决此问题。我们表明导致主要的转录变化,导致多谱系引发的基因表达状态在第一个细胞周期中非常迅速地发生。2个稳定的谱系启动模式之一在每个单元中以可变的时间逐渐出现。一些细胞在第一个细胞周期结束时达到稳定的形态和分子表型,并克隆地传播。其他一些在几个细胞周期内在两种表型之间波动。

更新日期:2017-08-03
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