1004 – REGULATION OF THE HEMATOPOIETIC STEM CELL POOL BY C-KIT-ASSOCIATED TROGOCYTOSIS

IF 2.5 4区医学 Q2 HEMATOLOGY Experimental hematology Pub Date : 2024-08-01 DOI:10.1016/j.exphem.2024.104305

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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Abstract

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.

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1004 - c-kit 相关逆转录细胞对造血干细胞池的调控

造血干细胞（HSCs）通常从骨髓（BM）动员到血液循环，用于临床移植。然而，人们还不了解单个干细胞离开骨髓的确切机制。这项研究确定了造血干细胞可动员池的细胞外在和分子决定因素。我们发现，有一部分造血干细胞的细胞表面显示与巨噬细胞相关的标记。这些造血干细胞在完全发挥功能的同时，会选择性地保留在龛位中，而缺乏巨噬细胞标记的干细胞则会在强制动员时离开BM。在小鼠和人类环境中，造血干细胞上的巨噬细胞标记可通过cKIT调控的逆行细胞吞噬作用，从驻留在BM中的巨噬细胞直接转移获得。我们的研究提供了成体干细胞利用逆行吞噬作用快速建立和激活功能调节分子机制的概念证明。

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来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

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.