Department of Bioengineering, Imperial College London, South Kensington Campus, London, United Kingdom.
Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom.
PLoS One. 2022 Sep 13;17(9):e0272587. doi: 10.1371/journal.pone.0272587. eCollection 2022.
Multi-potent progenitor (MPP) cells act as a key intermediary step between haematopoietic stem cells and the entirety of the mature blood cell system. Their eventual fate determination is thought to be achieved through migration in and out of spatially distinct niches. Here we first analyze statistically MPP cell trajectory data obtained from a series of long time-course 3D in vivo imaging experiments on irradiated mouse calvaria, and report that MPPs display transient super-diffusion with apparent non-Gaussian displacement distributions. Second, we explain these experimental findings using a run-and-tumble model of cell motion which incorporates the observed dynamical heterogeneity of the MPPs. Third, we use our model to extrapolate the dynamics to time-periods currently inaccessible experimentally, which enables us to quantitatively estimate the time and length scales at which super-diffusion transitions to Fickian diffusion. Our work sheds light on the potential importance of motility in early haematopoietic progenitor function.
多能祖细胞 (MPP) 作为造血干细胞和整个成熟血细胞系统之间的关键中间步骤。人们认为它们的最终命运决定是通过在空间上不同的小生境中进出迁移来实现的。在这里,我们首先对从一系列对辐照小鼠颅骨的长时程 3D 体内成像实验中获得的 MPP 细胞轨迹数据进行统计分析,并报告 MPP 显示出短暂的超扩散,具有明显的非高斯位移分布。其次,我们使用一种包含 MPP 观察到的动态异质性的细胞运动的跑和停留模型来解释这些实验发现。第三,我们使用我们的模型将动力学外推到目前实验无法达到的时间段,这使我们能够定量估计超扩散向菲克扩散过渡的时间和长度尺度。我们的工作揭示了运动在早期造血祖细胞功能中的潜在重要性。