High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.
High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.
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DOI：
10.1038/ncomms12169
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发表时间：
2016-07-18
影响因子：
16.6
通讯作者：
Reya T
中科院分区：
文献类型：
--
作者：
Koechlein CS;Harris JR;Lee TK;Weeks J;Fox RG;Zimdahl B;Ito T;Blevins A;Jung SH;Chute JP;Chourasia A;Covert MW;Reya T
虽然我们知道很多关于造血干/祖细胞的表型和功能，一个主要的挑战一直是在生命系统中映射它们的动态行为。在这里，我们描述了一种策略，以图像细胞在体内具有高的空间和时间分辨率，并量化它们的相互作用，使用高通量的计算方法。使用这些工具，和一个新的Msi 2报告模型，我们表明，造血干/祖细胞显示优先的空间亲和力接触血管龛，并与这些细胞的稳定协会的时间亲和力。随着细胞成熟，这些偏好明显减弱，这表明控制分化状态的程序是时空行为的关键决定因素，因此决定了细胞从特定微环境域接收的信号。这些共同表明，高分辨率成像与计算分析相结合可以提供新的生物学见解，并且从长远来看可以在其原生微环境中创建动态细胞图谱。 造血干细胞（HSC）在它们的小生境中成像是困难的。在这里，作者提出了一种新的高通量计算方法，以高空间和时间分辨率可视化体内HSC，并使用Msi 2报告分子标记内源性HSC和祖细胞，从而实现细胞跟踪
Although we know a great deal about the phenotype and function of haematopoietic stem/progenitor cells, a major challenge has been mapping their dynamic behaviour within living systems. Here we describe a strategy to image cells in vivo with high spatial and temporal resolution, and quantify their interactions using a high-throughput computational approach. Using these tools, and a new Msi2 reporter model, we show that haematopoietic stem/progenitor cells display preferential spatial affinity for contacting the vascular niche, and a temporal affinity for making stable associations with these cells. These preferences are markedly diminished as cells mature, suggesting that programs that control differentiation state are key determinants of spatiotemporal behaviour, and thus dictate the signals a cell receives from specific microenvironmental domains. These collectively demonstrate that high-resolution imaging coupled with computational analysis can provide new biological insight, and may in the long term enable creation of a dynamic atlas of cells within their native microenvironment. It is difficult to image haematopoietic stem cells (HSC) in their niche. Here, the authors present a new high-throughput computational approach to visualise HSCs in vivo at a high spatial and temporal resolution and also use a Msi2-reporter to label endogenous HSCs and progenitors, enabling cell tracking