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通过定量长期活细胞成像揭示造血过程中血细胞分化的动力学。

Kinetics of blood cell differentiation during hematopoiesis revealed by quantitative long-term live imaging.

机构信息

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada.

School of Biomedical Engineering, University of British Columbia, Vancouver, Canada.

出版信息

Elife. 2023 Mar 31;12:e84085. doi: 10.7554/eLife.84085.

Abstract

Stem cells typically reside in a specialized physical and biochemical environment that facilitates regulation of their behavior. For this reason, stem cells are ideally studied in contexts that maintain this precisely constructed microenvironment while still allowing for live imaging. Here, we describe a long-term organ culture and imaging strategy for hematopoiesis in flies that takes advantage of powerful genetic and transgenic tools available in this system. We find that fly blood progenitors undergo symmetric cell divisions and that their division is both linked to cell size and is spatially oriented. Using quantitative imaging to simultaneously track markers for stemness and differentiation in progenitors, we identify two types of differentiation that exhibit distinct kinetics. Moreover, we find that infection-induced activation of hematopoiesis occurs through modulation of the kinetics of cell differentiation. Overall, our results show that even subtle shifts in proliferation and differentiation kinetics can have large and aggregate effects to transform blood progenitors from a quiescent to an activated state.

摘要

干细胞通常存在于一种特殊的物理和生化环境中,这种环境有利于调节其行为。出于这个原因,干细胞在维持这种精确构建的微环境的同时,仍然允许进行活体成像的情况下,是最适合进行研究的。在这里,我们描述了一种在果蝇中造血的长期器官培养和成像策略,该策略利用了该系统中可用的强大的遗传和转基因工具。我们发现,果蝇血液祖细胞经历对称细胞分裂,其分裂既与细胞大小有关,又与空间方向有关。我们使用定量成像技术同时追踪祖细胞中干性和分化的标记物,确定了两种具有不同动力学的分化类型。此外,我们发现感染诱导的造血激活是通过调节细胞分化的动力学来实现的。总的来说,我们的结果表明,即使增殖和分化动力学的微小变化也会产生很大的累积效应,从而使血液祖细胞从静止状态转变为激活状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dd/10065797/8af36651045a/elife-84085-fig1.jpg

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