Intravital Imaging Reveals Motility of Adult Hematopoietic Stem Cells in the Bone Marrow Niche

被引:56
作者
Upadhaya, Samik [1 ]
Krichevsky, Oleg [2 ]
Akhmetzyanova, Ilseyar [3 ]
Sawai, Catherine M. [1 ,4 ]
Fooksman, David R. [3 ]
Reizis, Boris [1 ]
机构
[1] NYU, Grossman Sch Med, Dept Pathol, New York, NY 10016 USA
[2] Ben Gurion Univ Negev, Phys Dept, IL-84105 Beer Sheva, Israel
[3] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[4] Univ Bordeaux, Bergonie Canc Inst, INSERM Unit 1218, ACTION Lab, F-33076 Bordeaux, France
基金
以色列科学基金会;
关键词
PROGENITOR CELLS; DYNAMICS; CXCR4; MOBILIZATION; TRACKING; MURINE;
D O I
10.1016/j.stem.2020.06.003
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Adult mammalian hematopoietic stem cells (HSCs) reside in the bone marrow (BM) but can be mobilized into blood for use in transplantation. HSCs interact with BM niche cells that produce growth factor c-Kit ligand (Kitl/SCF) and chemokine CXCL12, and were thought to be static and sessile. We used two- photon laser scanning microscopy to visualize genetically labeled HSCs in the BM of live mice for several hours. The majority of HSCs showed a dynamic non-spherical morphology and significant motility, undergoing slow processive motion interrupted by short stretches of confined motion. HSCs moved in the perivascular space and showed intermittent close contacts with SCF-expressing perivascular stromal cells. In contrast, mobilization-inducing blockade of CXCL12 receptor CXCR4 and integrins rapidly abrogated HSC motility and shape dynamics in real time. Our results reveal an unexpectedly dynamic nature of HSC residence in the BM and interaction with the SCF+ stromal niche, which is disrupted during HSC mobilization.
引用
收藏
页码:336 / +
页数:14
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