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Developmental biology - Immune Cells|
Some blood stem cells are better than others
To test the contributions of these uniquely labelled blood stem cells, the scientists performed a series of bone marrow transplantations in mice. Mice received a combination of normal blood stem cells and deficient blood stem cells with a genetic mutation that prevented them from producing either B cells only, or both B and T cells.
Scientists found that the normal blood stem cells compensated for the B and T cell deficiencies.
Also, researchers found that a few specific blood stem cells were doing most of the work. These key blood stem cells proliferated dramatically, compensating for any immune cell deficiency in recipient mice, and continued proliferating even when transplanted into different recipient mice. These highly productive blood stem cells showed changes in gene activity that enhanced their ability to oversupply deficient types of immune cells.
"These stem cells' ability to compensate provides some degree of resilience to disruptions of the blood and immune system — as found in aging, the early stages of many blood disorders and cancers, and bone transplantation. By understanding and ultimately harnessing this innate capacity of stem cells, we can potentially optimize treatments for a wide range of diseases."
In most organ systems, regeneration is a coordinated effort that involves many stem cells, but little is known about whether and how individual stem cells compensate for the differentiation deficiencies of other stem cells. Functional compensation is critically important during disease progression and treatment. Here, we show how individual hematopoietic stem cell (HSC) clones heterogeneously compensate for the lymphopoietic deficiencies of other HSCs in a mouse. This compensation rescues the overall blood supply and influences blood cell types outside of the deficient lineages in distinct patterns. We find that highly differentiating HSC clones expand their cell numbers at specific differentiation stages to compensate for the deficiencies of other HSCs. Some of these clones continue to expand after transplantation into secondary recipients. In addition, lymphopoietic compensation involves gene expression changes in HSCs that are characterized by increased lymphoid priming, decreased myeloid priming, and HSC self-renewal. Our data illustrate how HSC clones coordinate to maintain the overall blood supply. Exploiting the innate compensation capacity of stem cell networks may improve the prognosis and treatment of many diseases.
Authors: Lisa Nguyen, Zheng Wang, Adnan Y Chowdhury, Elizabeth Chu, Jiya Eerdeng, Du Jiang, Rong Lu
Funding came from the National Institutes of Health (R00HL113104, R01HL135292, R01HL138225, P30CA014089, T32HD060549, and F31HL134359), the Rose Hills Foundation Science and Engineering Fellowship, the USC Provost’s Undergraduate Research Fellowship, the California Institute for Regenerative Medicine Training Grant, the Hearst Fellowship Award, the USC Office of Research, and the Norris Medical Library.
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A healthy T cell. Image credit: National Institute of Allergy and Infectious Diseases.