Xin Gao , Randall Carpenter , Philip Boulais , Dachuan Zhang , Christopher Marlein , Huihui Li , Matthew Smith , David Chung , Maria Maryanovich , Britta Will , Ulrich Steidl , Paul Frenette
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1004 – REGULATION OF THE HEMATOPOIETIC STEM CELL POOL BY C-KIT-ASSOCIATED TROGOCYTOSIS
Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. While fully functional, these HSC are selectively niche-retained as opposed to stem cells lacking macrophage markers which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer via trogocytosis, regulated by cKIT, from BM-resident macrophages in mouse and human settings. Our study provides proof-of-concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.
期刊介绍:
Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.