Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and homing to the bone marrow

Katharina Helene Susek; Eva Korpos; Jula Huppert; Chuan Wu; Irina Savelyeva; Frank Rosenbauer; Carsten Müller-Tidow; Steffen Koschmieder; Lydia Sorokin

doi:10.1016/j.matbio.2018.01.007

Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and homing to the bone marrow

Matrix Biol. 2018 Apr:67:47-62. doi: 10.1016/j.matbio.2018.01.007. Epub 2018 Jan 31.

Authors

Katharina Helene Susek¹, Eva Korpos¹, Jula Huppert¹, Chuan Wu², Irina Savelyeva³, Frank Rosenbauer⁴, Carsten Müller-Tidow⁵, Steffen Koschmieder⁶, Lydia Sorokin⁷

Affiliations

¹ Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany.
² Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany; Experimental Immunology Branch, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
³ Institute of Molecular Tumor Biology, University of Muenster, Germany.
⁴ Cells-in-Motion Cluster of Excellence, University of Muenster, Germany; Institute of Molecular Tumor Biology, University of Muenster, Germany.
⁵ Cells-in-Motion Cluster of Excellence, University of Muenster, Germany; Department of Medicine A-Hematology, Oncology and Pneumology, University Hospital Muenster, Germany; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg Germany.
⁶ Cells-in-Motion Cluster of Excellence, University of Muenster, Germany; Department of Medicine A-Hematology, Oncology and Pneumology, University Hospital Muenster, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
⁷ Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, Germany. Electronic address: sorokin@uni-muenster.de.

Abstract

Hematopoietic stem and progenitor cell (HSPC) functions are regulated by a specialized microenvironment in the bone marrow - the hematopoietic stem cell niche - of which the extracellular matrix (ECM) is an integral component. We describe here the localization of ECM molecules, in particular the laminin α4, α3 and α5 containing isoforms in the bone marrow. Laminin 421 (composed of laminin α4, β2, γ1 chains) is identified as a major component of the bone marrow ECM, occurring abundantly surrounding venous sinuses and in a specialized reticular fiber network of the intersinusoidal spaces of murine bone marrow (BM) in close association with HSPC. Bone marrow from Lama4^-/- mice is significantly less efficient in reconstituting the hematopoietic system of irradiated wildtype (WT) recipients in competitive bone marrow transplantation assays and shows reduced colony formation in vitro. This is partially due to retention of Lin^-c-kit⁺Sca-1⁺CD48^- long-term and short-term hematopoietic stem cells (LT-HSC/ST-HSC) in the G0 phase of the cell cycle in Lama4^-/- bone marrow and hence a more quiescent phenotype. In addition, the extravasation of WT BM cells into Lama4^-/- bone marrow is impaired, influencing the recirculation of HSPC. Our data suggest that these effects are mediated by a compensatory expression of laminin α5 containing isoforms (laminin 521/522) in Lama4^-/- bone marrow. Collectively, these intrinsic and extrinsic effects lead to reduced HSPC numbers in Lama4^-/- bone marrow and reduced hematopoietic potential.

Keywords: Bone marrow; Hematopoietic stem and progenitor cells (HSPC); Laminin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow / metabolism*
Cell Cycle
Cell Movement
Extracellular Matrix / metabolism
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / metabolism
Laminin / genetics
Laminin / metabolism*
Mice
Stem Cell Niche

Substances

Laminin

Grants and funding

ZIA BC011755/ImNIH/Intramural NIH HHS/United States