Samik Upadhaya1, Oleg Krichevsky2, Ilseyar Akhmetzyanova3, Catherine M Sawai4, David R Fooksman5, Boris Reizis6. 1. Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA. 2. Physics Department, Ben Gurion University of the Negev, Beer-Sheva 84105, Israel. 3. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 4. Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; INSERM Unit 1218 ACTION Laboratory, University of Bordeaux, Bergonié Cancer Institute, 33076 Bordeaux, France. 5. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: david.fooksman@einsteinmed.org. 6. Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA. Electronic address: boris.reizis@nyulangone.org.
Abstract
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.
Adult mammalian hematopoietic stem cells (pan class="Gene">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.
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