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As people age or become ill, their immune systems can become exhausted and less capable of fighting off viruses such as the flu or COVID-19. A recent mouse study has revealed just how specific gene activity could potentially enhance immune cell production. Published in Science Advances, this groundbreaking research is coming from the USC Stem Cell lab of Rong Lu.
“Hematopoietic stem cells, or HSCs, produce blood and immune cells, but not all HSCs are equally productive,” said the study’s corresponding author Rong Lu, Ph.D., who is an associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at USC, and a Leukemia & Lymphoma Society Scholar. “We wanted to understand the mechanism of why some stem cells produce more immune cells, while other stem cells produce fewer.”
In an effort to achieve this goal, Du Jiang, Ph.D., the first author of the study, and his colleagues at the Keck School of Medicine of USC have pioneered new techniques for understanding the quantitative association between immune cell production and gene expression in lab mice. This involved the labeling of individual stem cells with genetic “barcodes” to effectively track their immune cell production and a correlation with gene expression activity. They also utilized innovative bioinformatics approaches to characterize their quantitative association.
Utilizing these advanced techniques, the scientists identified nearly 40 genes—including genes associated with diseases such as myelodysplastic syndrome, a type of cancer caused by abnormal blood-forming cells—that are related to immune cell production.
The research revealed associations between the activity of these genes and both the quantity and variety of immune cells produced, shedding light on the distinct roles of genes in immune cell production. Certain genes are more associated with the production of lymphoid cells while others with myeloid cells, and some with a healthy balance of various immune cell types.
Moreover, through the study, a few genes demonstrated a “constant association” with the production of lymphocytes only. Continuing with their findings, some genes displayed a “discrete association” with the production of lymphocytes only. Finally, most commonly, genes would have either a “unimodal or multimodal” association with immune cell production—a significant discovery that promises to inform strategies to optimize bone marrow transplantation.
“In this study, we show that most genes associated with immune cell production are associated only at specific levels of immune cell production,” said Jiang, who earned his Ph.D. in the Lu Lab. “Our findings can inform strategies to optimize bone marrow transplantation—for example, by selecting donor bone marrow cells with gene activity associated with high and balanced levels of immune cell production.”
Additional authors include Adnan Y.