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Developmental biology - Immune Cells

Some blood stem cells are better than others

If some blood stem cells fail to do their part, other blood stem cells pick up their slack...

In your body, blood stem cells produce approximately 10 billion new white blood cells, also known as immune cells, each and every day. Even more remarkably, if some of these blood stem cells fail to do their part, then other blood stem cells pick up their slack and overproduce whichever specific type of immune cell is lacking, according to a new University of Southern California (USC) Stem Cell study published in the journal EMBO Reports.

USC PhD student Lisa Nguyen and colleagues in the laboratory of Rong Lu PhD, observed this phenomenon by tracking individual blood stem cells residing in the bone marrow of mice.
To create the tracking labels, scientists attached a unique piece of genetic code to each blood stem cell. During blood production, each blood stem cell passes its unique genetic label onto its progeny — which include two types of immune cells, known as B cells and T cells.

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.

When co-transplanted with B-deficient stem cells, normal stem cells overproduced B cells to keep the immune system in balance.

And when co-transplanted with B- and T-deficient stem cells, normal stem cells again compensated by overproducing both B and T cells to restore a balanced immune system.

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."

Rong Lu PhD, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA.

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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Jun 11, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

A healthy T cell. Image credit: National Institute of Allergy and Infectious Diseases.

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