Cincinnati Children's-led research team details how bone marrow response in mice varies by stress type and by type of bone, opening new paths for treating blood cancers, infections and moreCINCINNATI, March 20, 2024 /PRNewswire/ -- Imagine being able to count the different types of blood cells being formed inside the tiny bones of a mouse and pinpointing the strings and clusters of cells within the bone marrow that are responsible for producing specific types of blood cells..

辛辛那提儿童领导的研究小组详细介绍了小鼠的骨髓反应如何因压力类型和骨骼类型而异，为治疗血癌、感染和更多疾病开辟了新途径。2024年3月20日，辛辛那提/新闻专线/——想象一下能够计算出小鼠小骨内形成的不同类型的血细胞，并精确定位骨髓内负责产生特定类型血细胞的细胞串和细胞簇。。

Continue Reading

继续阅读

New study in the journal Nature, led by experts at Cincinnati Children's, reveals unprecedented cell-by-cell detail of how the bone marrow's blood production process works, and how different forms of stress affect production sites.

由辛辛那提儿童医院的专家领导的《自然》杂志上的一项新研究揭示了骨髓血液生产过程如何运作以及不同形式的压力如何影响生产部位的前所未有的细胞细节。

That's exactly what a team of scientists led by experts at Cincinnati Children's achieved in a far-reaching study published March 20, 2024, in the prestigious journal Nature. Their work adds unprecedented new understanding of the 'elegant' and 'resilient' anatomy of bone marrow while also generating evidence of unexpected variations in how the skeleton responds to stresses such as infection or blood loss..

这正是由辛辛那提儿童基金会专家领导的一组科学家在2024年3月20日发表在著名期刊《自然》上的一项意义深远的研究中取得的成就。他们的工作对骨髓的“优雅”和“弹性”解剖结构增加了前所未有的新理解，同时也产生了骨骼如何应对感染或失血等压力的意外变化的证据。。

'Stunningly, we found that the response to hematopoietic insults varies across the skeleton. We speculate that certain bones have specialized to preferentially respond to some insults, and this will be the focus of future studies,' the co-authors state.

“令人惊讶的是，我们发现骨骼对造血损伤的反应各不相同。合著者表示：“我们推测，某些骨骼专门对某些侮辱做出优先反应，这将成为未来研究的重点。”。

The research was led by co-first authors Qingqing Wu, PhD, and Jizhou Zhang, PhD, and corresponding author Daniel Lucas, PhD, all with the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. Overall, 23 researchers from five institutions contributed to this groundbreaking study.The discovery of specific blood cell production sites within the bone marrow raises new challenges and opportunities for diagnosing and treating a number of blood-related conditions.'For example, our data shows that biopsies that draw marrow from just one type of bone may not provide a full picture of how the blood production system has been affected by a disease or other insult,' Lucas says.

这项研究由第一作者吴青青（Qingqing Wu）博士和张纪洲（Jizhou Zhang）博士以及通讯作者丹尼尔·卢卡斯（Daniel Lucas）博士领导，他们都是辛辛那提儿童医院实验血液学和癌症生物学系的成员。总的来说，来自五个机构的23名研究人员为这项开创性的研究做出了贡献。骨髓中特定血细胞产生位点的发现为诊断和治疗许多与血液有关的疾病带来了新的挑战和机遇。”例如，我们的数据显示，仅从一种骨骼中提取骨髓的活组织检查可能无法全面了解血液生产系统如何受到疾病或其他侮辱的影响，”卢卡斯说。

'Meanwhile, efforts to stimulate production of certain blood cell types may be dramatically improved by focusing on specific bone types.'Highlights of the findingsThe key discoveries reported in the paper include:.

“同时，通过专注于特定的骨骼类型，刺激某些血细胞类型产生的努力可能会大大改善。”发现的亮点本文报道的关键发现包括：。

New tools allowing visualization of blood production inside the bone, allowing defining the basic anatomy of blood cell formation. These revealed that bone marrow functions are highly responsive and durable, but not uniform. The paper describes how strings and clusters of cells form within the marrow to act as blood cell production factories..

新的工具可以可视化骨骼内的血液生成，从而可以定义血细胞形成的基本解剖结构。这些表明骨髓功能具有高度的反应性和持久性，但并不均匀。本文描述了骨髓中如何形成细胞串和细胞簇，作为血细胞生产工厂。。

Location matters, even during normal blood cell production. The team demonstrated that different key types of progenitor cells move through different microenvironments as they mature. These microenvironments significantly influence which types of mature blood cells get produced. Different microenvironments give rise to oxygen-carrying red blood cells versus infection-fighting white blood cells, and so on..

即使在正常的血细胞生产过程中，位置也很重要。该团队证明，不同关键类型的祖细胞在成熟时会穿过不同的微环境。这些微环境显着影响产生哪种类型的成熟血细胞。不同的微环境产生携氧红细胞与抗感染白细胞等。。

Unexpected variations in stress responses. The researchers compared how the system responded to three acute kinds of stress: blood loss, L. monocytogenes infection, and granulocyte-colony stimulating factor (G-CSF) treatment (often given to boost white blood cell production after chemotherapy). They also measured how aging changed the process..

压力反应的意外变化。研究人员比较了该系统对三种急性应激的反应：失血、单核细胞增生李斯特菌感染和粒细胞集落刺激因子（G-CSF）治疗（通常用于化疗后促进白细胞产生）。他们还测量了衰老如何改变这一过程。。

The team meticulously measured how different bones responded to these insults. Among several examples: blood loss triggered rapid red blood cell production in the sternum, tibia, vertebrae, and humerus -- but not in the skull. Blood loss also temporarily reduced the number of B cell production sites across the skeleton.Meanwhile, when exposed to G-CSF, long bones rapidly increased formation of granulocyte progenitors and mature neutrophils.

研究小组仔细测量了不同骨骼对这些侮辱的反应。例如：失血会引发胸骨、胫骨、椎骨和肱骨中的红细胞快速产生，但不会在颅骨中产生。失血还暂时减少了整个骨骼中B细胞产生位点的数量。同时，当暴露于G-CSF时，长骨迅速增加粒细胞祖细胞和成熟中性粒细胞的形成。

But in sharp contrast, the sternum from the same mice displayed 'profound reductions' in these cell types as well as loss of neutrophil production sites.'These variations are important because until now, mouse studies of blood cell biology have depended almost entirely upon material collected from the femur and tibia,' Lucas says.Innovation required just to conduct the studyThe research team first needed to conduct a research project-within-the-project to establish a method for imaging and counting the different cell types at work within the mouse bone marrow. Counting the cells involved a process called confocal imaging microscopy.

但与之形成鲜明对比的是，同一只小鼠的胸骨显示出这些细胞类型的“大幅减少”以及中性粒细胞产生位点的丧失卢卡斯说，这些变异很重要，因为到目前为止，小鼠对血细胞生物学的研究几乎完全依赖于从股骨和胫骨收集的材料。进行这项研究需要创新研究团队首先需要在项目中进行一个研究项目，以建立一种成像和计数小鼠骨髓中不同细胞类型的方法。计数细胞涉及一个称为共聚焦成像显微镜的过程。

This uses specialized microscopes relying on lasers to detect specific tags in the cells. When 'tagged' properly, the cells  emit different colors under the laser, which allows them to be imaged and counted.The challenge is coming up with the right tag so that the laser accurately detects the targeted cells of interest, while not counting other cells.  In this study, the team started with a vast library of potential markers, then they whittled the list down to 35 promising genetic markersUltimately, they found that detecting cells that express the gene marker ESAM, in combination with other markers, allowed distinguishing between six different types of blood progenitor cells.

它使用专门的显微镜，依靠激光检测细胞中的特定标签。正确“标记”后，细胞在激光下发出不同的颜色，从而可以对其进行成像和计数。挑战在于找到正确的标签，以便激光能够准确检测目标细胞，同时不计算其他细胞。在这项研究中，该团队从一个庞大的潜在标记库开始，然后他们将列表缩小到35个有希望的遗传标记。最终，他们发现检测表达基因标记ESAM的细胞，结合其他标记，可以区分六种不同类型的血祖细胞。

The marker also proved capabl.

该标记也证明了capabl。