Functional compensation between hematopoietic stem cell clones in vivo

EMBO Reports
Lisa NguyenRong Lu

Abstract

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.

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Citations

Jan 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rong LuIrving L Weissman
Mar 7, 2020·Nature Protocols·Charles BramlettRong Lu
Dec 16, 2019·Drug Discovery Today·Labe Black, Tatiana Zorina
Jun 22, 2021·Radiation Research·J SaundersJ Palis

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