Home Medizin Studie zeigt, dass die Genaktivität eine Schlüsselrolle bei der Produktion von Immunzellen spielt

Studie zeigt, dass die Genaktivität eine Schlüsselrolle bei der Produktion von Immunzellen spielt

von NFI Redaktion


As people age or become ill, their immune system may become depleted and less able to fend off viruses such as the flu or COVID-19. In a new mouse study, partly funded by the National Institutes of Health and published in Science Advances, researchers from the USC Stem Cell Lab of Rong Lu describe how specific gene activity may potentially boost the production of immune cells.

Hematopoietic stem cells or HSCs produce blood and immune cells, but not all HSCs are equally productive. We wanted to understand the mechanism behind why some stem cells produce more immune cells, while others produce fewer.“

Rong Lu, PhD, corresponding author of the study, Associate Professor of Stem Cell Biology and Regenerative Medicine, Biomedical Engineering, Medicine, and Gerontology at USC, and Leukemia & Lymphoma Society Fellow

With this goal in mind, lead author Du Jiang, PhD, and his colleagues in the Lu Lab at the Keck School of Medicine at USC developed new techniques to understand the quantitative relationship between the production of immune cells and gene expression in laboratory mice. The scientists tagged individual stem cells with genetic „barcodes“ to track their immune cell production. They then correlated the barcode tracking with measurements of gene expression activity. They also developed innovative bioinformatic approaches to characterize their quantitative association.

By using these technical advances, the researchers 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 the production of immune cells. They discovered associations between the activity of these genes and both the quantity and diversity of the immune cells produced. For example, certain genes are associated with the production of lymphoid cells, others with myeloid cells, and still others with a healthy balance of different types of immune cells.

Some of the genes showed what the scientists described as „constant association“ with only the production of lymphocytes. In other words, at every level of lymphocyte production, gene expression was consistently associated with lymphocyte production.

Some other genes had only a „discrete association“ with the production of lymphocytes. This means that gene activity was linked to lymphocyte production within a specific range of lymphocyte production levels.

Most commonly, genes displayed either „unimodal or multimodal“ association with the production of immune cells. In these cases, involving both lymphoid and myeloid cells, gene activity was associated with the production of immune cells only at one or more specific levels of immune cell production.

„In this study, we show that most genes associated with the production of immune cells are only associated with specific levels of immune cell production,“ said Jiang, who earned his doctorate in the Lu Lab. „Our findings can impact strategies for optimizing bone marrow transplantation – for example, by selecting donor bone marrow cells with gene activity linked to high and balanced immune cell production.“

Other authors include Adnan Y. Chowdhury, Anna Nogalska, Jorge Contreras, Yeachan Lee, Mary Vergel-Rodriguez, and Melissa Valenzuela from the Lu Lab.

The project was supported by federal funding from the National Institutes of Health (grants R00HL113104, R01HL138225, R01HL135292, R01HL135292-S1, R35HL150826, and R01AG080982) and the National Cancer Institute (grant P30CA014089). Additional support came from the Leukemia & Lymphoma Society (grant LLS-1370-20), the California Institute for Regenerative Medicine, and the Hearst Foundations.

Source:

Keck School of Medicine at USC

Journal Reference:

Jiang, D., et al. (2024). Quantitative relationship between gene expression and blood cell production by individual hematopoietic stem cells in mice. Science Advances. doi.org/10.1126/sciadv.adk2132

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