As individuals age or change into in poor health, their immune techniques can change into exhausted and fewer able to combating off viruses such because the flu or COVID-19. In a brand new mouse examine funded partially by the Nationwide Institutes of Well being and revealed in Science Advances, researchers from the USC Stem Cell lab of Rong Lu describe how particular gene exercise might probably improve immune cell manufacturing.
“Hematopoietic stem cells, or HSCs, produce blood and immune cells, however not all HSCs are equally productive,” stated the examine’s corresponding writer Rong Lu, PhD, who’s an affiliate professor of stem cell biology and regenerative medication, biomedical engineering, medication, and gerontology at USC, and a Leukemia & Lymphoma Society Scholar. “We wished to grasp the mechanism of why some stem cells produce extra immune cells, whereas different stem cells produce fewer.”
With this aim in thoughts, first writer Du Jiang, PhD, and his colleagues within the within the Lu Lab on the Keck Faculty of Drugs of USC pioneered new methods for understanding the quantitative affiliation between immune cell manufacturing and gene expression in lab mice. The scientists labeled particular person stem cells with genetic “barcodes” to trace their immune cell manufacturing. They then correlated the barcode monitoring with measurements of gene expression exercise. Additionally they developed progressive bioinformatics approaches to characterize their quantitative affiliation.
By leveraging these technical advances, the scientists recognized practically 40 genes — together with genes related to ailments comparable to myelodysplastic syndrome, a sort of most cancers brought on by irregular blood-forming cells — which can be associated to immune cell manufacturing. They found associations between the exercise of those genes and each the amount and number of immune cells produced. For instance, sure genes are related to the manufacturing of lymphoid cells, others with myeloid cells, and nonetheless others with a wholesome steadiness of varied immune cell sorts.
Just a few of the genes confirmed what the scientists described as a “fixed affiliation” with the manufacturing of lymphocytes solely. In different phrases, at any degree of lymphocyte output, gene expression was at all times related to lymphocyte manufacturing.
Just a few different genes had a “discrete affiliation” with the manufacturing of lymphocytes solely. Because of this gene exercise was related to lymphocyte manufacturing inside a selected vary of lymphocyte output ranges.
Mostly, genes would have both a “unimodal or multimodal” affiliation with immune cell manufacturing. In these cases, which concerned each lymphoid and myeloid cells, gene exercise was solely related to immune cell manufacturing at both one or a number of particular ranges of immune cell manufacturing.
“On this examine, we present that almost all genes related to immune cell manufacturing are related solely at particular ranges of immune cell manufacturing,” stated Jiang, who earned his PhD within the Lu Lab.”Our findings can inform methods to optimize bone marrow transplantation — for instance, by deciding on donor bone marrow cells with gene exercise related to excessive and balanced ranges of immune cell manufacturing.”
Further authors embrace Adnan Y. Chowdhury, Anna Nogalska, Jorge Contreras, Yeachan Lee, Mary Vergel-Rodriguez, and Melissa Valenzuela from the Lu Lab.
The undertaking was supported by federal funding from the Nationwide Institutes of Well being (grants R00HL113104, R01HL138225, R01HL135292, R01HL135292-S1, R35HL150826, and R01AG080982) and the Nationwide Most cancers Institute (grant P30CA014089). Further help got here from the Leukemia & Lymphoma Society (grant LLS-1370-20), California Institute for Regenerative Drugs, and the Hearst Foundations.
