小柯机器人

美国波士顿市儿童医院Fernando D. Camargo和波士顿麻省总医院Charles P. Lin合作的最新研究开发了天然造血干细胞（HSC）和祖细胞的活动物成像技术。这一研究成果在线发表在2020年2月5日的国际学术期刊《自然》上。

研究人员创立了小鼠双重遗传技术，该技术是指将报告标签标注在一群静态的长期HSC（LT-HSC），并且与目前颅骨骨髓中活体成像方法兼容。研究表明，这群LT-HSCs靠近前置血管和骨内膜表面。相比之下，多能祖细胞（MPP）与内膜的距离变化更大，并且更可能与过渡区血管相关。LT-HSCs在最缺氧的骨髓壁中未发现，而是在与MPP相似的低氧环境中被发现。体内延时成像显示，处于稳态的LT-HSC具有限的运动能力。激活的LT-HSC具有异质性，一些细胞变得高度活跃，而一部分HSC在空间受限的区域内克隆扩增。这些结构域具有明确的特点，因为HSC扩增几乎完全在具有骨重塑活性的骨髓腔细胞群中发现。相比之下，具有低骨吸收活性的腔则不会容纳不断扩增的HSC。这些发现揭示了之前未知的事实，即骨骼更新阶段决定了骨髓微环境内的异质性。该方法可以直接可视化HSC行为并可以区分HSC龛的异质性。

据了解，对造血干细胞的生物学研究主要是在移植条件下进行的。据科学家介绍研究动态HSC行为具有挑战性，因为尚不能在自然状态的活体动物中实现HSC的可视化。

附：英文原文

Title: Live-animal imaging of native haematopoietic stem and progenitor cells

Author: Constantina Christodoulou, Joel A. Spencer, Shu-Chi A. Yeh, Raphal Turcotte, Konstantinos D. Kokkaliaris, Riccardo Panero, Azucena Ramos, Guoji Guo, Negar Seyedhassantehrani, Tatiana V. Esipova, Sergei A. Vinogradov, Sarah Rudzinskas, Yi Zhang, Archibald S. Perkins, Stuart H. Orkin, Raffaele A. Calogero, Timm Schroeder, Charles P. Lin, Fernando D. Camargo

Issue&Volume: 2020-02-05

Abstract: The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow3,4,5. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.

DOI: 10.1038/s41586-020-1971-z

Source: https://www.nature.com/articles/s41586-020-1971-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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