How The Pressure Affects Molecular Mechanism of Bone Marrow Hematopoietic Function

Hematopoiesis is affected by biological stresses, such as infections, inflammation, and specific drugs. Recently, in a research report published in the international journal of Blood, scientists from Tokyo Medical and Dental University identified a new type of cell surface marker through research, which can help accurately analyze the response of the hematopoietic process to biological stress.

Hematopoiesis includes the generation of three types of blood cells, namely red blood cells, white blood cells, and platelets, which is a dynamic process of response to disease processes inside and outside the bone marrow, and the bone marrow is the place where blood cells are generated. Previously, scientists' research on hematopoiesis mainly relied on the protein Sca-1, which is expressed by hematopoietic stem cells and early hematopoietic progenitor cells. These two types of cells are common progenitor cells of the three types of blood cells. Although most of the advanced progenitor cells for each blood cell do not express Sca-1, recent studies have increasingly found that these cells will begin to express Sca-1 again under biological stress, which will reduce the reliability of hematopoietic analysis based on Sca-1 expression.

CD86

The corresponding author Toshiaki Ohteki said that accurate analysis of hematopoiesis is essential for understanding the pathological progress and characteristics of various diseases. The goal of this study is to identify a reliable marker that can be used to study the body's hematopoietic response to stress. In the article, the researchers injected a bacterial toxin into mice to induce systemic bacterial infections, and meanwhile, an increase in the level of Sca-1 positive hematopoietic progenitor cells being detected which indicates that Sca-1 negative cells will start expressing the protein to deal with the infection.

In order to identify the excellent markers of Sca-1, the researchers screened 180 cell surface proteins and finally found that CD86 protein can be used as a new candidate marker. Compared with Sca-1, in the context of systemic bacterial infection, the expression of CD86 does not increase significantly, which confirms the potential of effectively distinguishing early and late hematopoietic stem cells under stress conditions.

So can CD86 really help understand the mechanism of biological stress affecting the body's hematopoietic response? The researchers focused on studying the process of erythropoiesis in mice injected with bacterial toxins, within 18-24 hours after toxin injection, CD86-based analysis can help researchers identify the early activation stage of erythropoiesis in the bone marrow while Sca-1-based molecules cannot be identified. After further research, the researchers found that the number of red blood cells in the bone marrow reached a peak at 18 hours, and then fell to the baseline level at 72 hours. On the contrary, the number of red blood cells in the blood will start to increase after 24 hours. Interestingly, the newly generated cells have the morphological characteristics of mature red blood cells, that is, smaller cell size and no nucleus, which indicates that these cells may not be precursor cells of red blood cells.

Finally, researcher Ohteki said that the results of this study revealed how CD86 can correct the deficiency of Sca-1 in the process of hematopoiesis. For further study, scientists may be able to utilize CD86 as an alternative Sca-1 biomarker to evaluate the true hematopoietic response under stress.  

Reference:

  1. Masashi Kanayama,Yuta Izumi,Yasuharu Yamauchi, et al. CD86-based analysis enables observation of bona fide hematopoietic responses, Blood (2020). DOI: 10.1182/blood.2020004923
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