How stress affects bone marrow

June 30, 2020

Researchers from Tokyo Medical and Dental University (TMDU) identify the protein CD86 as a novel marker of infection- and inflammation-induced hematopoietic responses

Tokyo, Japan - Hematopoiesis can be affected by biological stresses, such as infection, inflammation and certain medications. In a new study, researchers from Tokyo Medical and Dental University (TMDU) identified a novel cell surface marker that enables the accurate analysis of hematopoietic responses to biological stress.

Hematopoiesis includes the production of all three types of blood cells: red blood cells, white blood cells, and platelets. It is a dynamic process that reacts to disease processes in and outside the bone marrow--the place where blood cells are produced. Previously, hematopoietic studies mainly relied on the analysis of the protein Sca-1, which is expressed by hematopoietic stem cells and early hematopoietic progenitor cells, both of which are common progenitors of all three types of blood cells. While Sca-1 is not expressed by most of late progenitor cells specific to one type of blood cell, recent reports have increasingly suggested that these cells start expressing Sca-1 again in times of biological stress (Figure 1), reducing the reliability of hematopoietic analyses based on Sca-1 expression.

"Accurate analysis of hematopoiesis is crucial to our understanding of the pathogenesis of various diseases," says corresponding author of the study Toshiaki Ohteki. "The goal of our study was to identify an alternative, stable marker that can be reliably used to study hematopoietic responses to stress situations."

To achieve their goal, Masashi Kanayama, a main contributor of this project, injected a bacterial toxin into mice to induce systemic bacterial infection and detected an increase of Sca-1-positive hematopoietic progenitor cells, suggesting that Sca-1-negative cells started expressing the protein as a response to infection. To identify a superior marker to Sca-1, he screened 180 cell surface proteins and identified the protein CD86 as a novel candidate marker. In contrast to Sca-1, CD86 expression did not increase significantly upon systemic bacterial infection (Figure 1), confirming its potential to distinguish early and late hematopoietic progenitor cells under stress conditions.

But could CD86 help understand how biological stress affects hematopoietic responses? To investigate this, the researchers focused on erythropoiesis, the production of red blood cells, in mice injected with the bacterial toxin. CD86-based analysis identified an early activation phase of erythropoiesis in the bone marrow within 18-24 hours after toxin injection, while Sca-1-based analysis did not. Further analysis showed that the number of red blood cells in the bone marrow peaked at 18 hours to then decreased to basal levels by 72 hours. Conversely, the number of red blood cells in the blood began to increase by 24 hours. Intriguingly, the researchers found that the newly produced cells had the morphological characteristics of mature red blood cells, that is, a smaller cell size and the absence of a nucleus, confirming that the cells were not red blood cell precursors.

"These are striking results that show how CD86 can rectify the shortcomings of Sca-1 in the analysis of hematopoiesis," says Ohteki. "Our findings provide new insights into the use of CD86 as an alternative marker to Sca-1 for assessing bona fide hematopoietic responses under stress conditions."
The article, "CD86-based analysis enables observation of bona fide hematopoietic responses," was published in Blood at DOI: 10.1182/blood.2020004923

Tokyo Medical and Dental University

Related Bone Marrow Articles from Brightsurf:

Researchers identify the mechanism behind bone marrow failure in Fanconi anaemia
Researchers at the University of Helsinki and the Dana-Farber Cancer Institute have identified the mechanism behind bone marrow failure developing in children that suffer from Fanconi anaemia.

Nanoparticles can turn off genes in bone marrow cells
Using specialized nanoparticles, MIT engineers have developed a way to turn off specific genes in cells of the bone marrow, which play an important role in producing blood cells.

How stress affects bone marrow
Researchers from Tokyo Medical and Dental University (TMDU) identified the protein CD86 as a novel marker of infection- and inflammation-induced hematopoietic responses.

3D atlas of the bone marrow -- in single cell resolution
Stem cells located in the bone marrow generate and control the production of blood and immune cells.

Dangerous bone marrow, organ transplant complication explained
Scientists have discovered the molecular mechanism behind how the common cytomegalovirus can wreak havoc on bone marrow and organ transplant patients, according to a paper published in the journal Cell & Host Microbe.

Viagra shows promise for use in bone marrow transplants
Researchers at UC Santa Cruz have demonstrated a new, rapid method to obtain donor stem cells for bone marrow transplants using a combination of Viagra and a second drug called Plerixafor.

Bone marrow may be the missing piece of the fertility puzzle
A woman's bone marrow may determine her ability to start and sustain a pregnancy, report Yale researchers in PLOS Biology.

Cells that make bone marrow also travel to the womb to help pregnancy
Bone marrow-derived cells play a role in changes to the mouse uterus before and during pregnancy, enabling implantation of the embryo and reducing pregnancy loss, according to research published Sept.

Uncovering secrets of bone marrow cells and how they differentiate
Researchers mapped distinct bone marrow niche populations and their differentiation paths for the bone marrow factory that starts from mesenchymal stromal cells and ends with three types of cells -- fat cells, bone-making cells and cartilage-making cells.

Zebrafish help researchers explore alternatives to bone marrow donation
UC San Diego researchers discover new role for epidermal growth factor receptor in blood stem cell development, a crucial key to being able to generate them in the laboratory, and circumvent the need for bone marrow donation.

Read More: Bone Marrow News and Bone Marrow Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to