A time- and single-cell-resolved model of murine bone marrow hematopoiesis.
A time- and single-cell-resolved model of murine bone marrow hematopoiesis.
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DOI：
10.1016/j.stem.2023.12.001
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发表时间：
2023-12
期刊：
影响因子：
23.9
通讯作者：
I. Kucinski;Joana Campos;Melania Barile;Francesco Severi;Natacha Bohin;Pedro N. Moreira;Lewis Allen-Lewis-All
中科院分区：
文献类型：
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作者：
I. Kucinski;Joana Campos;Melania Barile;Francesco Severi;Natacha Bohin;Pedro N. Moreira;Lewis Allen-Lewis-All
典型的造血树模型被越来越多地认识到是有限的，因为它是基于在很大程度上由测试细胞命运潜力的非稳态分析定义的异质种群。在这里，我们将持续标记和时间序列单细胞RNA测序相结合，建立了一个实时、定量的小鼠骨髓造血组织动力学模型。我们将级联单细胞表达模式与分化和生长速度的动态变化结合在一起。由此产生的分子状态和细胞行为之间的显性联系揭示了不同谱系之间广泛不同的自我更新和分化特性。移植的干细胞在红系和中性粒细胞产生的特定阶段表现出强烈的分化加速，说明了该模型如何量化扰动的影响。我们根据快照测量重建动态行为类似于动态显像仪如何将连续的图像合并到电影中。我们假设这种方法普遍适用于在高分辨率下理解组织尺度的动力学。
The paradigmatic hematopoietic tree model is increasingly recognized to be limited, as it is based on heterogeneous populations largely defined by non-homeostatic assays testing cell fate potentials. Here, we combine persistent labeling with time-series single-cell RNA sequencing to build a real-time, quantitative model ofin vivotissue dynamics for murine bone marrow hematopoiesis. We couple cascading single-cell expression patterns with dynamic changes in differentiation and growth speeds. The resulting explicit linkage between molecular states and cellular behavior reveals widely varying self-renewal and differentiation properties across distinct lineages. Transplanted stem cells show strong acceleration of differentiation at specific stages of erythroid and neutrophil production, illustrating how the model can quantify the impact of perturbations. Our reconstruction of dynamic behavior from snapshot measurements is akin to how a kinetoscope allows sequential images to merge into a movie. We posit that this approach is generally applicable to understanding tissue-scale dynamics at high resolution.