Scientists from Cincinnati Children’s Hospital Medical Center, Massachusetts General Hospital, and elsewhere have been able to pinpoint cells in mouse bone marrow that give rise to specific types of blood cells. They also found evidence of variations in how the skeleton responds to stressors such as infection or blood loss. Details of the findings are published in a new Nature paper titled, “Resilient anatomy and local plasticity of naive and stress haematopoiesis.”
The study was led by co-first authors Qingqing Wu, PhD, and Jizhou Zhang, PhD, and corresponding author Daniel Lucas, PhD, all with Cincinnati Children’s Division of Experimental Hematology and Cancer Biology. According to the paper, they and their colleagues used confocal imaging microscopy to detect and image cells expressing specific genetic markers including ESAM, which is expressed in all hematopoietic stem cells. The technology enabled them to distinguish between six different types of blood progenitor cells. They also captured information about the bone marrow’s microenvironment and analyzed blood cell development in multiple parts of the skeleton.
For the study, the researchers looked at how different types of blood cells are made in mouse bone marrow under normal and stressful states. Among other discoveries, the researchers identified strings and clusters of cells in bone marrow that act as factories for blood cell production, and found that these continue to work in the same way in both normal and stressed solutions. These blood cell production sites present new challenges and opportunities for diagnosing and treating various blood-related conditions, according to the researchers.
“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 noted. “Meanwhile, efforts to stimulate production of certain blood cell types may be dramatically improved by focusing on specific bone types.”
Also reported in the paper is the finding that different progenitor cells move through different microenvironments as they mature. The research also showed that the microenvironments influence the types of mature blood cells—including red blood cells and white blood cells—that get produced.
The researchers also looked at how different bones in the mouse skeletal system responded to acute stress namely blood loss, Listeria monocytogenes infection, and treatment with granulocyte-colony stimulating factor (G-CSF), which is given to boost white cell production after chemotherapy.
The results showed that bone marrow in different parts of the skeleton responded differently when stressed. Specifically, some parts made more blood cells in response to stressors while other parts seemed unaffected. For example, blood loss triggered rapid red blood cell production in the sternum, tibia, vertebrae, and humerus—but not in the skull. Meanwhile, blood loss temporarily reduced the number of B-cell production sites across the skeleton. When the bone marrow was exposed to G-CSF treatment, long bones formed more granulocyte progenitors and mature neutrophils. In contrast, sternum bones showed “profound reductions” in these cell types as well as loss of neutrophil production sites.
For their next steps, the researchers plan to explore further how different parts of the skeleton specialize in producing specific blood components. They will also look into how much of the bone marrow stress response that they observed in the mice also occurs in humans.
