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Zon, Leonard I., M.D. 2019

Researcher Profiles

Researcher Profiles

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Leonard I. Zon, M.D.

Leonard I. Zon, M.D.

Boston Children's Hospital

2019 Funding recipient

Role of macrophages in remodeling hematopoietic stem cell clonal architecture and in progression from clonal hematopoiesis to MDS

Discovery Research Grant 2019

PROJECT SUMMARY

The aim of this project is to study interactions between blood stem cells and macrophages, a type of immune cell, during development. Visualizing the embryonic blood system in zebrafish reveals that macrophages and blood stem cells have very intimate physical contact during the first few days of life. We see that macrophages engage blood stem cells and either fully engulf the stem cell or remove portions of cellular material. When the numbers of embryonic macrophages are reduced, the number of blood stem cells that contribute to long-term blood production is reduced, indicating that the macrophage interactions may be important. When we analyzed genes expressed and proteins found in macrophages, we identified candidate factors that decorate the surface of the stem cell and corresponding receptors on the macrophages. When we reduce levels of the stem cell factor, we see a reduction in the interactions with macrophages, a loss of stem cell divisions, and a reduction in the number of stem cells that contribute to adult blood. Increasing levels of this factor on stem cells leads to an increase in macrophage interactions. Understanding the connection between these macrophage interactions, this surface molecule, and stem cell divisions will be beneficial in improving stem cell therapies through transplantation.

PUBLICATIONS

Wattrus SJ, Smith ML, Rodrigues CP, Hagedorn EJ, Kim JW, Budnik B, Zon LI, Quality Assurance of Hematopoietic Stem Cells by Macrophages Determines Stem Cell Clonality, Science, 2022, 377 (6613), 1413–1419 DOI: 10.1126/science.abo4837
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    • FUNDING INFORMATION
    • CENTERS FOR MDS
  • EVANS MDS SUMMIT
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