英国剑桥大学Berthold Göttgens，英国伦敦玛丽女王大学Kamil R. Kranc和英国爱丁堡大学Dónal O'Carroll共同合作，近期取得重要工作进展。他们研究开发了小鼠骨髓造血的时间和单细胞分辨模型。相关研究成果2024年1月5日在线发表于《细胞—干细胞》杂志上。

据介绍，典型的造血层级结构模型越来越被认为是有限的，因为它基于异质群体，主要由测试细胞命运潜力的非稳态分析定义。

研究人员将持续标记与时间序列单细胞RNA测序相结合，建立了小鼠骨髓造血的体内组织动力学的实时定量模型。研究人员将级联单细胞表达模式与分化和生长速度的动态变化相结合。由此产生的分子状态和细胞行为之间的明确联系，揭示了不同谱系之间广泛变化的自我更新和分化特性。

移植的干细胞在红细胞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。研究人员从快照测量中重建动态行为，类似于电影放映机如何将连续图像合并到电影中。

总之，研究人员认为这种方法通常适用于以高分辨率理解组织尺度动力学。

附：英文原文

Title: A time- and single-cell-resolved model of murine bone marrow hematopoiesis

Author: Iwo Kucinski, Joana Campos, Melania Barile, Francesco Severi, Natacha Bohin, Pedro N. Moreira, Lewis Allen, Hannah Lawson, Myriam L.R. Haltalli, Sarah J. Kinston, Dónal OCarroll, Kamil R. Kranc, Berthold Gttgens

Issue&Volume: 2024-01-05

Abstract: 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 of in vivo tissue 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.

DOI: 10.1016/j.stem.2023.12.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00431-9